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Archive for the ‘IPS Cell Therapy’ Category

Reprogrammed cells relieve Parkinson’s symptoms in trials – Nature.com

B. Bick, . Poindexter, UT Med. School/SPL

A depletion of brain cells that produce dopamine is responsible for the mobility problems seen in people with Parkinsons disease.

Japanese researchers report promising results from an experimental therapy for Parkinsons disease that involves implanting neurons made from reprogrammed stem cells into the brain. A trial conducted in monkeys with a version of the disease showed that the treatment improved their symptoms and seemed to be safe, according to a report published on 30 August in Nature1.

The studys key finding that the implanted cells survived in the brain for at least two years without causing any dangerous effects in the body provides a major boost to researchers hopes of testing stem-cell treatments for Parkinsons in humans, say scientists.

Jun Takahashi, a stem-cell scientist at Kyoto University in Japan who led the study, says that his team plans to begin transplanting neurons made from induced pluripotent stem (iPS) cells into people with Parkinsons in clinical trials soon.

The research is also likely to inform several other groups worldwide that are testing different approaches to treating Parkinsons using stem cells, with trials also slated to begin soon.

Nature breaks down the latest research and what it means for the future of stem-cell treatments.

Parkinsons is a neurodegenerative condition caused by the death of cells called dopaminergic neurons, which make a neurotransmitter called dopamine in certain areas of the brain. Because dopamine-producing brain cells are involved in movement, people with the condition experience characteristic tremors and stiff muscles. Current treatments address symptoms of the disease but not the underlying cause.

Researchers have pursued the idea that pluripotent stem cells, which can form any cell type in the body, could replace dead dopamine-making neurons in people with Parkinsons, and thus potentially halt or even reverse disease progression. Embryonic stem cells, derived from human embryos, have this capacity, but they have been the subject of ethical debates. Induced pluripotent stem (iPS) cells, which are made by coaxing adult cells into an embryonic-like state, have the same versatility without the associated ethical concerns.

Takahashis team transformed iPS cells derived from both healthy people and those with Parkinsons into dopamine-producing neurons. They then transplanted these cells into macaque monkeys with a form of the disease induced by a neuron-killing toxin.

The transplanted brain cells survived for at least two years and formed connections with the monkeys brain cells, potentially explaining why the monkeys treated with cells began moving around their cages more frequently.

Crucially, Takahashis team found no sign that the transplanted cells had developed into tumours a key concern with treatments that involve pluripotent cells or that they evoked an immune response that couldnt be controlled with immune-suppressing drugs.

Its addressing a set of critical issues that need to be investigated before one can, with confidence, move to using the cells in humans, says Anders Bjorklund, a neuroscientist at Lund University in Sweden.

I hope we can begin a clinical trial by the end of next year, says Takahashi. Such a trial would be the first iPS cell trial for Parkinson's. In 2014, a Japanese woman in her 70s became the first person to receive cells derived from iPS cells, to treat her macular degeneration.

In theory, iPS cells could be tailor-made for individual patients, which would eliminate the need to use drugs that suppress a possible immune response to foreign tissues.

But customized iPS cells are expensive to make and can take a couple months to derive and grow, Takahashi notes. So his team instead plans to establish iPS cell lines from healthy people and then use immune cell biomarkers to match them to people with Parkinsons in the hope of minimizing the immune response (and therefore the need for drugs to blunt the attack).

In a study described in an accompanying paper in Nature Communications2, Takahashis team implanted into monkeys iPS-cell-derived neurons from different macaques. They found that transplants between monkeys carrying similar white blood cell markers triggered a muted immune reaction.

Earlier this year, Chinese researchers began a Parkinsons trial that used a different approach: giving patients neural-precursor cells made from embryonic stem cells, which are intended to develop into mature dopamine-producing neurons. A year earlier, in a separate trial, patients in Australia received similar cells. But some researchers have expressed concerns that the immature transplanted cells could develop tumour-causing mutations.

Meanwhile, researchers who are part of a Parkinsons stem-cell therapy consortium called GForce-PD, of which Takahashis team is a member, are set to bring still other approaches to the clinic. Teams in the United States, Sweden and the United Kingdom are all planning trials to transplant dopamine-producing neurons made from embryonic stem cells into humans. Previously established lines of embryonic stem cells have the benefit that they are well studied and can be grown in large quantities, and so all trial participants can receive a standardized treatment, notes Bjorklund, also a consortium member.

Jeanne Loring, a stem-cell scientist at the Scripps Research Institute in La Jolla, California, favours transplanting iPS-derived neurons made from a patients own cells. Although expensive, this approach avoids dangerous immunosuppressive drugs, she says. And because iPS cells are established anew for each patient, the lines go through relatively few cell divisions, minimizing the risk that they will develop tumour-causing mutations. Loring hopes to begin her teams trial in 2019. This shouldnt be a race and were cheering for success by all, she says.

Lorenz Studer, a stem-cell scientist at the Memorial Sloan Kettering Cancer Center in New York City who is working on a trial that will use neurons made from embryonic stem cells, says that there are still issues to work out, such as the number of cells needed in each transplant procedure. But he says that the latest study is a sign that we are ready to move forward.

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Reprogrammed cells relieve Parkinson's symptoms in trials - Nature.com

Wasteful spending on medical public works – The Japan Times

Social security expenditures keep rising endlessly as the aging of Japans population accelerates with the low birthrate. Yet, little is known about the way huge sums of taxpayer money are being poured into wasteful projects tied to vested interests in the name of saving human lives.

The Japan Agency for Medical Research and Development (AMED), which Prime Minister Shinzo Abe created with much fanfare in 2015 as a counterpart to the U.S. National Institute of Health, has an annual budget in excess of 140 billion. But the National Cancer Center (NCC), which is supposed to be a major recipient of the AMED fund, is in trouble because excessive sums have been spent on construction of buildings and facilities in the name of life science research.

A glance at the NCCs financial statements shows that its retained earnings plummeted from 5.6 billion in fiscal 2010 to 762 million in 2015. The steep fall in the retained earnings is not due to cuts in grants from the Health, Labor and Welfare Ministry, as a high-ranking NCC official claims. The NCC earned 31.4 billion from medical services and 4.3 billion from research projects in fiscal 2010, and these earnings rose by 41 percent to 44.4 billion and 14 percent to 9.2 billion, respectively, unequivocally showing that the rise in earnings far exceeded the cut in government grants.

Then why have its retained earnings fallen so rapidly? The answer is that excessive investments in construction of new facilities have eaten into its funds. For example, it cost 5.4 billion to build a new research center on next-generation surgery and endoscopy, which was completed in May, and another 16.7 billion to build a new research laboratory that began operating in July. The question here is not the sheer sum spent on these projects, but their balance with the institutes earnings. During the 2010-16 period, money spent on such construction projects exceeded the NCCs operating income by 44.3 billion. It seems clear that the NCC is investing beyond its means even as construction costs surge ahead of the 2020 Tokyo Olympic Games.

Cases of advanced medicine becoming an arena for big spending like public works projects are also found in the field of heavy particle therapy. Japan has five institutions specializing in this field, the pioneer among them being the National Institute of Radiological Sciences in Chiba Prefecture. The number in Japan represents nearly half of the 11 such facilities now operating worldwide.

The five heavy particle therapy facilities are located in Chiba, Hyogo, Gunma, Saga and Kanagawa prefectures, with one more being planned in Yamagata. And oddly enough, though, the NCC supposedly the control tower of cancer therapy in Japan has no such institute. That is said to be because those institutes were located in facilities with close links to the Education, Culture, Sports, Science and Technology Ministry which took the lead in the development of heavy particle therapy instead of the health ministry.

One reason why Gunma University has one of those institutes is not because the university excelled in cancer treatment but, according to a source familiar with the decision, because of the influence of former education minister Hirofumi Nakasone, an Upper House member elected from the Gunma constituency and a powerful member of the Liberal Democratic Partys education lobby. Gunma Prefecture was eager to have the facility established there because that involved heavy initial investments about 7 billion each for the buildings and radiation equipment providing huge economic benefits to local construction and other related industries.

Haphazard ways in which money is being spent on advanced medical research are also found in the projects for biobanks, institutions that collect and preserve biospecimens of people such as blood, urine and DNA samples. Through followup research on the registered people and linking with their clinical information, their activities are expected to contribute to identifying the causes of illnesses and developing new medicines.

Of a number of biobanks set up in Japan, the Tohoku Medical Megabank Organization at Tohoku University is by far the largest. It started operating in fiscal 2011 as part of a series of government projects for recontruction from the Great East Japan Earthquake and tsunami that hit the regions Pacific coast. In its initial year of operation, more than 10 billion from the government budget was poured into the Tohoku Medical Megabank. A total of 5.1 billion was spent on the construction and design of a seven-story complex and another 7.5 billion on its facilities and equipment in the years through fiscal 2013. While spending was scaled back in subsequent years, 4.5 billion has been set aside for the project in fiscal 2017 a sum equivalent to the funding allocated to Kyoto University for its research on iPS (induced pluripotent stem) cells.

Tohoku Medical Megabank is staffed with 32 professors, 10 associate professors and 25 instructors. However, some of the staff are deemed not necessarily fit for the types of work assigned to the institute, leading some students to comment sarcastically that those who have failed to be promoted to full professorship at Tohoku University have been given new jobs at the biobank. Moreover, the quality of some of the work performed by the institute has been called into question.

The value of biobank is determined by the quality of the data obtained by its research. If the quality is poor, such an institute would not be trusted by researchers in pharmaceutical companies or other institutes. Six years after its creation, Tohoku Medical Megabanks achievement remains poor in terms of significant research that would have lured pharmaceutical firms and others to collaborate with the institute. The head of the biobank is not deterred, however, as he says his institutes research projects take time before tangible results can be produced, and the institute keeps asking for more funding from the AMED.

As funding for Tohoku Medical Megabank gets prioritized, budgetary allocations for the more prestigious BioBank Japan, which has been jointly established by the government-affiliated Riken research institute and the University of Tokyos Institute of Medical Science, has been significantly reduced. The budget cut by AMED is about to deal a fatal blow to the institute that has played a leading role in genome research in Japan.

Given Japans dire fiscal conditions, government funding on scientific research cannot be an exception to budget cuts. Time will come sooner or later for the generous funding for Tohoku Medical Megabank to be curtailed. Today, however, huge sums of taxpayer money are being poured on the institute despite its poor records of significant achievements in the name of the reconstruction of the areas ravaged by the 2011 disasters. Along with the spending of taxpayer money, new positions are being created for post-retirement jobs for government bureaucrats.

The circumstances surrounding those advanced medical research institutes look similar to those involving the governments public works projects: Securing funding from taxpayer money becomes more important than the outcome of projects. Unless the structure is fixed, there will be no hope of medical science becoming a core of the governments growth strategy.

This is an abridged translation of an article from the August issue of Sentaku, a monthly magazine covering political, social and economic scenes. More English articles can be read at http://www.sentaku-en.com

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Wasteful spending on medical public works - The Japan Times

For Immune System Stem Cell Studies, Mice Aren’t Enough – Science 2.0

If mouse studies were transferable to humans, we'd have cured every disease thousands of times. That is the big reason why you shouldn't accept scaremongering about the chemical of the week in the New York Times, or claims about Miracle Vegetables in the Washington Post.

Stem cell therapy is all the rage, with suspect companies sprouting up like supplement stores, claiming to be a benefit for this and that. Often all they have are mouse studies and FDA disclaimers on their side. That's not to say mouse studies are not valuable, they eliminate a lot of bad products, and in some instances mouse models are good analogues of humans, like in HIV infection, but a new paper reveals what chemists have long known: When it comes to the immune system rats are not little people, even "humanized" mice whichhave been engineered to have a human, rather than a murine, immune system.

These animals have been used for decades to study things like the immune response to the transplantation of pancreatic islet cells for diabetes and skin grafts for burn victims. But unlike what would occur in a human patient, the humanized mice are unable to robustly reject the transplantation of genetically mismatched human stem cells. As a result, they can't be used to study the immunosuppressive drugs that patients will likely require after transplant. The researchers conclude that the humanized mouse model is not suitable for studying the human immune response to transplanted stem cells or cells derived from them.

"In an ideal situation, these humanized mice would reject foreign stem cells just as a human patient would," said Joseph Wu, MD, PhD, director of Stanford University School of Medicine's Cardiovascular Institute and professor of cardiovascular medicine and of radiology. "We could then test a variety of immunosuppressive drugs to learn which might work best in patients, or to screen for new drugs that could inhibit this rejection. We can't do that with these animals."

The researchers write in Cell Reports that they were studying pluripotent stem cells, which can become any tissue in the body. They tested the animals' immune response to human embryonic stem cells, which are naturally pluripotent, and to induced pluripotent stem cells. Although iPS cells can be made from a patient's own tissues, future clinical applications will likely rely on pre-screened, FDA-approved banks of stem cell-derived products developed for specific clinical situations, such as heart muscle cells to repair tissue damaged by a heart attack, or endothelial cells to stimulate new blood vessel growth. Unlike patient-specific iPS cells, these cells would be reliable and immediately available for clinical use. But because they won't genetically match each patient, it's likely that they would be rejected without giving the recipients immunosuppressive drugs.

The authors found that two varieties of humanized mice were unable to completely reject unrelated human embryonic stem cells or iPS cells, despite the fact that some human immune cells homed to and were active in the transplanted stem cell grafts. In some cases, the cells not only thrived, but grew rapidly to form cancers called teratomas. In contrast, mice with unaltered immune systems quickly dispatched both forms of human pluripotent stem cells.

The researchers obtained similar results when they transplanted endothelial cells derived from the pluripotent stem cells.

A new mouse model

To understand more about what was happening, they created a new mouse model similar to the humanized mice. Instead of reconstituting the animals' nonexistent immune systems with human cells, however, they used immune and bone marrow cells from a different strain of mice. They then performed the same set of experiments again.

Unlike the humanized mice, these new mice robustly rejected human pluripotent stem cells as well as mouse stem cells from a genetically mismatched strain of mice. In other words, their newly acquired immune systems appeared to be in much better working order.

Although more research needs to be done to identify the cause of the discrepancy between the two types of animals, the researchers speculate it may have something to do with the complexity of the immune system and the need to further optimize the humanized mouse model to perhaps include other types of cells or signaling molecules. In the meantime, they are warning other researchers of potential pitfalls in using this model to screen for immunosuppressive drugs that could be effective after human stem cell transplants.

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For Immune System Stem Cell Studies, Mice Aren't Enough - Science 2.0

An Experts Perspective on Accelerated Pathways for Cell …

Yaron Ramati, Director of Regulatory Affairs at Pluristem Therapeutics

Over the past few years, the regulatory landscape for cell therapy development has grown increasingly complex. There are now accelerated pathways for advanced therapy medicinal products (ATMPs) in several countries worldwide, including the U.S., Japan, and South Korea. While the possibility for accelerated commercialization has resulted from these changes, substantial complexity has also been introduced, making it a more elaborate process to move cell therapy products from bench to bedside.

In the interview with Yaron Ramati, Director of Regulatory Affairs at Pluristem Therapeutics, we get an experts perspective on how the regulatory environment has changed and new opportunities that exist for bringing cell therapy products through the clinical trial process and into the global marketplace.

Yaron Ramati: I have 10 years of experience in regulatory affairs in biotechnology companies in Israel.

I have a PhD in Philosophy of Biology from the London School of Economics and an M.Sc. from the Technion in Neurobiology

Yaron Ramati:The United States, Japan, and South Korea are countries that have accelerated pathways that are unique for cell and gene therapies. Legislation took effect in Japan in late 2014, in South Korea in 2016, and in the United States in 2017.

Additionally, the EU has a program for product acceleration the Adaptive Pathways. Although it is not explicitly for cell and gene therapies, these have been given a lot of attention by the group.

Yaron Ramati:

In the United States: Regenerative medicine advanced therapy (RMAT) designation.Cell therapies that aim to treat serious medical conditions with high unmet need, and have preliminary favorable clinical data, can get the designation. It allows for accelerated approval (i.e., the use of biomarkers and intermediate endpoints for BLA, priority review).

In Japan: Conditional time-limited marketing authorization.This program allows for regenerative therapies (cell, gene and tissue therapies) to receive conditional marketing authorization for up to 7 years, following confirmation of safety and an initial proof of efficacy in Japan in diseases that are serious and have a high unmet need.

In South Korea: Conditional marketing authorization for cell therapy.As in Japan, this program allows for cell therapies to receive conditional marketing authorization for a limited time, following an initial proof of efficacy in serious diseases.

In EU: Adaptive Pathways pilot program. This program is a pilot program established by the EMA to explore ways in which the EMA can assist the streamlining the development of new promising therapies for serious conditions with high unmet need. Although this program is not explicitly for cell or gene therapy, it is the main focus of the group.

Yaron Ramati: All EU countries have a joint definition for ATMPs as set by EU regulation. Other countries have separate definitions that only partially overlap.

Yaron Ramati: Only few countries in the world are willing to be the first to provide marketing authorization for novel therapies. For ATMPs, European regulation does not allow individual countries in the union to provide marketing authorization, and so the EMA is the only gateway for ATMPs in Europe.

The U.S. FDA, Japan PMDA, and South Korea KFDA are the only others that are willing to be first to approve ATMPs.

Yaron Ramati: Currently, the EMA and PMDA are leading with four marketing approvals of cell and gene therapies each. RMAT designation procedure in the U.S. is expecting to give a boost to the products that are being developed for the U.S. market.

Yaron Ramati: Pluristem is very active in the field of accelerated development of its products. PLX-PAD of Pluristem has been accepted to the Japan conditional time-limited marketing authorization scheme by PMD, as well as to the adaptive pathways program of the EMA. It is active in both programs.

In addition, Pluristem intends to make use of the accelerated pathways offered for regenerative therapies in both the U.S. and in South Korea.

Yaron Ramati: The focus of Pluristem in these programs is the advancement of PLX-PAD. Pluristem had achieved understandings with EMA and PMDA regarding the accelerated approval of PLX-PAD for the treatment of critical limb ischemia (CLI).

It is the intention of Pluristem to achieve similar understandings with FDA, EMA, PMDA and KFDA regarding the development of PLX-PAD for the treatment of patients following hip fractures.

Yaron Ramati: PLX-PAD was accepted into the EMA adaptive pathways pilot program in 2015. Since then, Pluristem has taken advantage of this program in coming to an understanding with the EMA on the desired regulatory path of PLX-PAD in CLI. In addition, Pluristem undertook parallel scientific advice with the EMA and leading health technology assessment (HTA) bodies in Europe.

In this meeting, Pluristem received valuable feedback on the expectations that these bodies have for purposes of reimbursement in Europe. Pluristem has designed the Phase 3 PACE study in CLI patients in view of the feedback received from both the EMA and the HTA bodies, with the purpose of addressing their respective expectations.

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Daiichi Sankyo hearts Cuorips – Global University Venturing

Cuorips, a Japan-based cardiac therapy developer spun out from Osaka University, has secured an undisclosed amount from pharmaceutical firm Daiichi Sankyo.

The investment was made as part of an agreement that gives the corporate an option right for the worldwide commercialisation of Cuorips technology, called iPS-derived cardiomyocyte sheet, a cell therapy for patients suffering from severe heart failure.

The treatment uses induced pluripotent stem (iPS) cells, which can be generated directly from a donors mature cells and differentiated into any organ. It offers an alternative to patients who would otherwise require a heart or artificial heart transplant.

The technology is based on research led by Yoshiki Sawa, professor at the Graduate School of Medicines Department of Cardiovascular Surgery.

Sawa developed the therapy through his participation in the Research Center Network for Realization of Regenerative Medicine, operated by the research organisation Japan Agency for Medical Research and Development.

Cuorips is currently gearing up for clinical research and an investigator-initiated clinical trial.

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Daiichi Sankyo hearts Cuorips - Global University Venturing

Daiichi Sankyo invests in Osaka University spin-off – The Pharma Letter (registration)

Japanese pharma major Daiichi Sankyo (TYO: 4568) revealed this morning that it has signed an investment contract with Cuorips Inc, an Osaka University spin-off venture to receive an option right concerning the worldwide commercialization of iPS-derived cardiomyocyte (iPS-CM) sheet developed by Cuorips.

The iPS-CM sheet is an allogeneic cell therapy product consisting of cardiomyocyte derived from human iPS cells. Its transplantation is expected to provide improvement of cardiac function and amelioration of heart failure and become a new treatment option for patients with severe heart failure, who have no remedies other than heart transplantation or artificial heart implantation.

Based on the cutting-edge cell therapy research targeting heart diseases, the team at the Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, led by Professor Yoshiki Sawa, has been working on the iPS-CM research and development by participating in the Research Center Network for Realization of Regenerative Medicine, which is run by the Japan Agency for Medical Research and Development (AMED). They are currently preparing for clinical research as well as investigator initiated clinical study.

Cuorips was founded to develop and commercialize iPS-CM sheets based on the research data and technologies developed by the university.

Daiichi Sankyo has been conducting research on iPS cell-derived cardiomyocyte and their production, and is currently working on the efficient production process capable for commercial supply. Daiichi Sankyo and Cuorips are aiming to commercialize iPS-CM sheets as a pioneering treatment for severe heart failure.

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Daiichi Sankyo invests in Osaka University spin-off - The Pharma Letter (registration)

Affimed Therapeutics’ (AFMD) CEO Adi Hoess on Q2 2017 Results – Earnings Call Transcript – Seeking Alpha

Affimed Therapeutics (NASDAQ:AFMD)

Q2 2017 Earnings Conference Call

August 1, 2017 8:30 AM ET

Executives

Anca Alexandru Head of Communications

Adi Hoess Chief Executive Officer

Florian Fischer Chief Financial Officer

Analysts

Maury Raycroft Jefferies

Do Kim BMO Capital Markets

Michael Schmidt Leerink

Peter Lawson SunTrust

Operator

Good day and welcome to the Affimed Second Quarter 2017 Financial Results and Corporate Update Conference Call. Todays conference is being recorded. At this time, I would like to turn the conference over to Anca Alexandru. Please go ahead.

Anca Alexandru

Thanks. I would like to welcome you to our investor and analyst call on the results for the second quarter of 2017. On the call with me today are Adi Hoess, CEO of Affimed, who will present the corporate update; and Florian Fischer, Affimeds CFO, who will walk you through the financials.

Slide 2, before we start, please note that this call and the Q&A session contains forward-looking statements, including statements regarding our future financial condition, business strategy, and our plans and objectives for our future operations.

These statements represent our beliefs and assumptions only as of the date of this discussion. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future.

These forward-looking statements are subject to risks and uncertainties and actual results may differ materially from those expressed or implied in the forward-looking statements due to various factors including, but not limited to those identified under the section entitled risk Factors in our filings with the SEC and those identified under the section entitled cautionary statements regarding forward-looking statements in our Form 6-K filed with the SEC earlier today.

Thank you for your understanding. I will now hand the call over to our CEO, Adi Hoess, who will provide the corporate update.

Adi Hoess

Thanks a lot, Anca. Affimed has developed an immune cell engager and our clinical and preclinical pipeline based on tetravalent bi and trispecificantibody formats. Were an industry leader in NK cell engagement and our lead product candidate AFM13 is to our knowledge, the most advanced NK-cell engager in clinical development.

We also have a well-differentiated T-cell based approach, which includes our clinical candidate AFM11 and well provide an update on these clinical programs as well as our pre-clinical programs today. We employ about 75 full time equivalents with our headquarter located in Heidelberg, Germany, and affiliate offices in the U.S., that is Affimed Inc., as well as our subsidiary AbCheck in Plze, in the Czech Republic.

Slide 4. We have an unencumbered clinical and pre-clinical pipeline of NK and T-cell engagers, with our NK-cell engagers being developed in hematological diseases and solid tumors. Based on our NK-cell platform, we have one clinical and two pre-clinical programs in developments. And based on our T-cell platform, we have one program in our own clinical development. And second T-cell engager program based on our platform called AMV564 is being developed by Amphivena, a company of which we own about 18.5% fully diluted. AMV564 has recently entered clinical development.

Slide 5 summarizes our second quarter updates for our NK cell engager program. For AFM13, we have completed the dose escalation part of our Phase 1b combination study with Mercks Keytruda in Hodgkin Lymphoma and initiated the expansion phase. The AFM13 Phase 2a monotherapy trial in Hodgkin Lymphoma sponsored by the German Hodgkin Study Group is open to recruit under new study design, which includes patients pre-treated with both brentuximab vedotin and anti-PD1.

Columbia University has recently initiated a translational study of AFM13 in CD30-positive lymphoma with cutaneous manifestation and I will provide more detail later. We made further progress in our collaboration with MD Anderson Cancer Center to evaluate AFM13 in combination with MD Andersons NK cell product. In June, we presented new data for our NK cell engagers AFM24 and AFM26 at two conferences and I will go into detail later on this.

Slide 6 summarizes the progress, we have made with our T-cell engager. Two Phase 1 dose-escalation studies are ongoing with AFM11, which offer a significant opportunity to address the high unmet medical need in diffuse large B-Cell lymphoma and mantle cell lymphoma. We believe that both the properties of AFM11 and the design of our studies can attract, specifically, mutations of other drugs in development.

Both dose escalation studies, which are conducted in ALL and in NHL respectively are designed with accelerated titration followed by a classical 3+3 design. In both studies, AFM11 was overall well tolerated with no dose limits and toxicity observed to date. In the AFM11 study in relapsed refractory ALL, which was initiated in September 2016, patients are currently being recruited into the fourth dose cohort. 12 sites are open and recruiting in the Czech Republic, Poland, Russia, Austria and Israel.

As mentioned, no DLTs were observed in particular no AFM11 related grade 3 or grade 4 neurotoxicity or side effects are frequently observed with T-cell engaging antibody agents observed. In our study of AFM11 in relapsed refractory NHL, patients are currently being recruited into the third dose cohort. Recall that this study has been amended in the past to enroll patients under a new revised study design.

We believe that we have addressed this lower than effective recruitment by opening further trial sites. A total of 10 sites are now opened in the Czech Republic, Poland, Germany as well as the U.S. Like in our ALL trial, no AFM11 related grade 3 or grade 4 neurotoxicity was observed to date under their revised study design. We intend to provide regular update on both the AFM11 studies in the future.

A second T-cell engager program based on our platform is AMV564, a bispecific tetravalent CD33/CD3 antibody developed by Amphivena in AML. A Phase 1 study is recruiting. However, no further updates have been provided by Amphivena.

Slide 7 shows our platform, which is very distinguished from others as, in contrast, the most comparatives were developing tetravalent bispecific molecules. The bivalent binding of two receptors on two different cells enables high-affinity binding through the avidity effect, which is advantageous to maintain high specificity at very high affinity.

We believe that this is very important in order to obtain a favorable safety profile. Furthermore, our platform allows multi-specificity in the tailored PK. Further differentiating Affimed, while most immune cell engaging approaches to date focus on T cells, our technology platform reliably generates both T and NK-cell engagers.

While increasingly NK-cells are becoming a cornerstone of cancer immunotherapy, and we're excited to be pioneering this development. There are a number of reasons why NK-cell-based approaches are very attractive and one of the reasons is that there seems to be a positive correlation between NK-cell infiltration and clinical outcome in patients.

In this context, it has been described that a low cytotoxicity is associated with higher incidence of cancer. In addition, recent clinical data show improved anti-tumor responses of ex vivo expanded and activated NK-cell populations. NK-cell-based immunotherapy has recently advanced with different treatment approaches, including engagers, check points, cytokines and adoptive cellular transfer.

To-date, it seems that NK-cell-based approaches have this strong advantage of controlling a well manageable favorable safety profile. This creates an opportunity for NK-cell redirection to address the lack of recognition of cancer cells and also allows for potential combination of NK-cells with other approaches to enhance efficacy.

A common theme in all different cancer types is the ability of the tumor cell to evade recognition by the immune system and, specifically, by NK-cells as shown on Slide 9. Normally, NK-cells are capable of killing foreign or aberrant cells, like tumor cells, have acquired mechanisms to escape the so-called immune surveillance.

As a result, such NK-cells cannot recognize tumor cells as foreign or aberrant and, therefore, cannot fight them. We believe that our platform has the potential to overcome these limitations by disabling the tumor evasion mechanisms, and I will explain on the next slide what this belief is based on.

Our expertise and leadership in natural-killer cell-based approaches is one of our key assets. As we can see here, there are a multitude of activating and inhibitory NK-cell receptors being discovered that CD16A, a dominant activating receptor on innate immune cells, is the only activating receptor that triggers the cytotoxic activity of nave human NK cells, even in the absence of costimulatory signals.

Based on these properties and on our preclinical and clinical data generated to date, we believe that targeting CD16A is key for efficient recruitment of and killing by NK cells and macrophages. We have secured a solid IP position around CD16A targets.

Slide 10. We believe that through targeting CD16A with high affinity and specificity, the significant limitations of IgGs can differ. With our tetravalent bispecific immune cell engagers, we can restore NK-cell killing in tumor immune control, and this is depicted here.

Let me explain in more detail why we believe that our approach is superior compared to IgG-based approaches. The human body is not using NK-cell engagement by IgG to eliminate cancer cells. However, this mechanism is used for cells infected by viruses or bacteria.

In this situation, the human immune system generates a collagen antibody response that highly decorates such infected cells or organisms.

Highly decorated means that many different proteins are expressed on the cell surface, which can then be found bound by antibodies. This polyclonal and high-density binding leads to NK-cells killing upon high avidity XP binding, plus antibodies for CD16A on the NK-cell and other XP gamma receptors, for example, CD32 and CD64.

In the setting of targetable cancer cells, however, with IgG, the situation is very different. Firstly, the therapeutic molecule targets a single epitope. Hence, it confers ammonia killing response. And secondly, there are cancer cells which express only very low numbers of the desired target.

The consequence of this very low target density is an insufficient amount of IgG, decorating the cancer cells and thereby not being able to efficiently recruit immune cells. This is shown in the middle picture. Interesting, most therapeutic monoclonal antibodies are target-modulating antibodies, such as cetuximab, polatuzumab, gevokizumab, just to mention a few of them.

We are addressing this limitation by targeting CD16A with high affinity and specificity, as shown. Indeed, our immune cell engagers has the potential to elicit a robust NK-cell killing and immune control due to multivalent and apparent high-affinity binding to CD16A even at limiting antigen densities on the target.

Slide 11, furthermore, CD16A in confers additional superior engager features. The binding of immune cells through CD16A with high affinity and specificity induces NK-cell activation, which triggers an integrated immune response that can be mediated by both innate and adaptive immune cells. In particular, our NK-cell engagers do not bind to CD16B and neutrophils, which avoids the sync effect. Their affinity has been demonstrated to be over 1,000 fold higher than that of monoclonal antibodies and our engagers bind independently of the 158 valine phenylalanine polymorphism.

Most importantly, theres virtually no competition with plasma IgG, which is shown here. In the ground stage, CD16A on innate immune cells is occupied by polyclonal plasma IgG. But there is a huge excess of plasma IgG versus therapeutic antibodies, this creates a significant threshold for FC-based therapeutic antibodies, however, not for CD16A target enhancement.

Our tetravalent and bispecific molecules, which recognize a different epitope from CD16A, are virtually unaffected by plasma IgG. All these unique features result in overall increased potency and efficacy of NK-cell engagers.

Slide 12. Our lead candidate, CD30/CD16A-specific NK-cell engager, AFM13 is a first-in-class antibody suitable for mono and combination therapy. This has demonstrated safety and clinical activity in heavily pretreated Hodgkin lymphoma patients in a Phase 1 study. In this Phase 1 study, tumor shrinkage and potential responses were observed in patients treated with four weekly doses of at least 1.5 mg/kg of AFM13. In 62% of patients, which was eight out of thirteen patients, we observed tumor shrinkage in 23% of patients, which was a total of three out of thirteen experienced partial response. None of the patients experiencing a PR had been previously treated with brentuximab vedotin.

Recall, that in our investigation the Phase 2a trial for AFM13 in relapsed and refractory Hodgkin lymphoma, which is led by the German Hodgkin Study Group, we have previously guided to change the study protocol to ensure a recruitment of a homogeneous patient population pre-treated with both BV and anti-PD1 antibodies. The study is now open to recruit under the new study design.

We had also provided some preliminary data from patients enrolled under the original study protocol, where partial responses were observed in two of seven evaluated patients who had been pre-treated with brentuximab vedotin, but were anti-PD1 naive. This suggests, now, for the first time that AFM13 is active as a single agent in this heavily pre-treated group of patients and, in particular, that AFM13 is active post brentuximab vedotin. We have learned from the study sponsor that both after-responders had failed BV as the most recent treatment prior to AFM13 therapy, with one patient experiencing stable disease and the other one partial in the progressive disease under the BV treatment.

As previously guided, full data from the ongoing study will be presented upon its anticipated completion in 2019. And prior to that, a decision of data publication time points will be made together with the German Hodgkin Study Group.

We are further developing AFM13 as a combination therapy. Preclinical affinity has been demonstrated in combination with anti-PD1 in vivo in a PDX model. This has been the basis of our Phase 1b trial in relapsed refractory Hodgkin lymphoma in combination with Mercks Keytruda. And here, we have completed the dose escalation part of the trial. In detail, three patients were enrolled into dose levels one and two, respectively, and six patients were enrolled into dose level three. While no grade three or four adverse events related to the study treatment were observed, one DLT was observed in cohort 3, which was a repeated grade two infusion-related reaction, leading to discontinuation of AFM13 treatment. This event is classified as a DLT according to the protocol definition. No further DLTs occurred.

The dose expansion cohort has been initiated with the highest dose explored during dose escalation. Data readout is ongoing in the treated cohort and we intend to present data from the dose escalation at a scientific medical conference in the second half of 2017.

Another update this quarter is that Columbia University has initiated a translational Phase 1b/2a study to evaluate the validity of activity of AFM13 in patients with relapsed and refractory CD30-positive lymphoma with cutaneous manifestation. Affirmed is supporting this trial which is designed to allow for serial biopsies, thereby enabling assessment of NK-cell biology and tumor cell killing within the tumor environment. The first patient was enrolled into the study in July 2017. In general, we view CD30-positive lymphoma as an attractive indication that may broaden the potential of AFM13. In terms of further guidance, we will work together with Columbia University to provide update on this study.

Slide 13. Additional opportunities for our NK-cell engagers include combinations with adoptive NK-cell transfer. Patients on NK cells can be stimulated by monotherapy using NK-cell engagers to overcome tumor immune evasion and immunosuppression. Ex vivo expansion and stimulation of autologous NK-cells followed by reinfusion alone or in combination with NK cell engager, is a viable therapeutic approach providing increased numbers of activated NK cells. Alternatively, NK cells can be derived from peripheral blood, cord blood or IPS cells from healthy donors, which is an allogeneic setting, or from immortalized cells. After ex vivo stimulation and expansion, the NK cells are infused into the patients in combination with NK cell engagers.

We are investigating this approach with our partner MD Anderson. Initially, we plan to investigate AFM13 with MDACCs NK-cell product in the transplant setting. Preclinical research activities are on track and these are intended to be followed by Phase 1 clinical trial. Proof-of-concept for this combination would also pave the way for combinations of other pipeline product such as for AFM23.

Affimed holds an option to exclusive worldwide rights to develop and commercialize any product developed under the collaboration. In addition to our clinical product candidates, we have created a strong preclinical pipeline. Over the last quarter we have further characterized our most advanced preclinical candidates, AFM24 and AFM26, which we are developing for three solid tumors and multiple myeloma respectively.

Despite several marketed agents such as cetuximab and tyrosine kinase inhibitor or TKIs, there is a significant medical need for a novel approach to treat EGF receptor-positive tumor. Both efficacy and toxicity can be addressed. EGFR-blocking drugs have been described to have side-effects including serious skin toxicity which might impact physicians willingness to prescribe a drug. In terms of efficacy, there is a need to overcome intrinsic or acquired resistance. For example, there is no clear indication of efficacy of EGFR-blocking antibodies in patients with RAS mutation.

We are developing a first-in-class NK cell engager designed to overcome the limitations of conventional therapy. AFM24 is designed to effectively treat EGFR-expressing solid tumors, such as lung and neck, or colon cancers. It is an EGFR/CD16A targeting tetravalent bispecific antibody that is well differentiated from cetuximab, it is more potent cytotoxicity in vitro and in vivo including a potential to kill RAS-mutant cell lines. There is novel mechanism of action in safety profile and it has the potential to overcome intrinsic or acquired resistance, which is described by many patients with EGFR positive tumors.

AFM24s potent NK cell recruitment may enable the shift of the validated target EGF receptor, primary receptor block toward immuno-oncology. We have identified several development candidates for which we have initiated IND-enabling studies.

Slide 15, there are several factors which differentiate AFM24 from other therapy. Firstly, AFM24 is differentiated through its efficacy. Here you can see that in vitro, our NK cell engager which is highly potent tumor cell killing independent of RAS mutational status. In vivo, we have demonstrated efficacy in tumors resistant to EGFR targeting agents. Importantly, as shown in the graphs on the right hand side, AFM24 was similarly efficacious in a cetuximab-sensitive model.

Secondly, AFM24 is differentiated through safety, Slide 16. We have completed pilot toxicity studies in cynomolgus monkeys with no major safety findings. At the EACR-AACR-SIC Special Conference, we presented data on a dose-range binder study in which AFM24 was dosed up to 93.75 mg/kg and a repeated dose study in which AFM24 was dosed up to 30 mg/kg in 4 weeks.

No AFM24-related macro or microscopic changes were seen in tissues including vital organs, skin and injection site. Importantly, there was no evidence of skin toxicity in those studies. Also no signs of delayed toxicity was observed in the repeated dose study recovery animals. On a molecular level, we learned from in vitro toxicology studies but there was no cytokine release or NK cell proliferation in the absence of target cells. This further substantiates AFM24s potential beneficial safety profile.

Slide 17, like for EGFR targeted tumors, there is a significant need for a novel approach to treat multiple myeloma. Even though, new therapies have significant improved outcomes, cure still remains elusive and the medical need to achieve minimal residual disease negativity is not yet addressed.

MRD positivity is associated with a poorer prognosis, and it has been recorded that persistent MRD by predictive marker of unsustained complete response. A particular hurdle for therapeutics aimed at immune cell engagement are very high M-protein serum levels up to 170mg/mL. Indeed the competition by serum IgG is known to strongly impair antibody-dependent cell-mediated cytotoxicity, the activity of monoclonal antibodies.

We are developing AFM26 to overcome the limitations of conventional therapies in multiple myeloma. AFM26 is a first-in-class tetravalent bispecific antibody targeting BCMA/CD16A. Targeting BCMA and employing NK cell engagement offers the potential to achieve MRD-negativity. For AFM26, NK cell binding is largely unaffected by circulating IgG, which creates the potential of NK cell activation in the presence of M-protein.

Indeed, the high affinity binding to both target and NK cells leads to a prolonged cell retention. This is shown on the right on the slide on the right bottom. AFM26 shows high cytotoxicity cytotoxic activity towards both low and high BCMA-expressing myeloma cells. AFM26 may be potentially safer than T cell-based approaches, which would allow for faster development timelines. Based on these characteristics, AFM26 might be positioned in first line of combination with adoptive NK-cell transfer during ASCT or in a salvage setting.

AFM26 binds the B-cell maturation antigen, which is an antigen ubiquitously expressed on malignant plasma cells. Its expression on healthy tissues is limited to plasma cells and peripheral dendritic cells. We believe the BCMA is an ideal target for immunotherapy of multiple myeloma.

At ASCO and at the EACR-AACR-SIC, both in June, well present the data on AFM26 NK-cell binding properties and activity. As shown here, these data underscore that compared to native and FC-enhanced IgG. AFM26 shows improved binding and cell surface retention.

Slide 20, we also show that AFM26 is well differentiated through target cell binding in potent NK-cell mediated tumor cell lysis. And this is shown here in comparison with two marketed agents, daratumumab and anti-CD38 antibody and elotuzumab, which targets PS1. Importantly, other than described for daratumumab and elotuzumab, AFM26 did not induce NK-cell mutation.

Slide 21, like our other NK-cell engagers, AFM26 is also well differentiated for other agents [indiscernible] safety. Here you can see that compared to a T-cell engager, AFM26 is similarly potent that shows a reduced cytokine release pattern. This point is going to improve safety profile, making AFM26 uniquely suited to engage NK-cells with multiple myeloma.

I will now hand over the call to our CFO, Florian Fischer, who will provide further details on the financial figures.

Florian Fischer

Thank you, Adi. Affimeds consolidated financial statements have been prepared in accordance with IFRS as issued by the International Accounting Standards Board or IASB. The consolidated financial statements are presented in euro, which is the companys functional and presentation currency. Therefore, all financial numbers that I will present here in this call unless otherwise noted will be in euros. Any numbers referring to Q2 2017 and Q2 2016 are unaudited.

Cash and cash equivalents and financial assets totaled 48.9 million as of June 2017 compared to 44.9 million as of December 31, 2016. The increase was primarily attributable to the net proceeds of 16.4 million from a public offering of common shares in the first quarter, and of 2.5 million from the drawdown of the second tranche of the loan from Silicon Valley Bank, largely offset by operational expenses.

Net cash used in operating activities was 13.1 million for the six months ended June 30, 2017compared to 17 million for the six months ended June 30, 2016. The decrease was primarily related to lower cash expenditure for research and development in connection with Affimeds development and collaboration programs and to the expiration of the Amphivena collaboration.

Affimed expects to have cash to fund our operations at least until the end of 2018. This provides runway for the planned development of our clinical programs, as well as for product discovery and early development activity.

Revenue for the second quarter of 2017 was 0.5 million compared to 2.1 million for the second quarter 2016. Revenue in the 2017 period was primarily derived from AbCheck services, while revenue in 2016 period predominantly to Affimeds collaboration with Amphivena.

R&D expenses for the second quarter of 2017 were 5.4 million compared to 8.6 million for the second quarter of 2016. The decrease was primarily related to lower expenses for AFM13 and our discovery and early stage development activities and the expiration of the Amphivena collaboration.

G&A expenses for the second quarter of 2017 were unchanged at 2.0 million compared to the second quarter of 2016. Net loss for the second quarter of 2017 was 7.9 million, or 0.18 per common share, compared to a net loss of 8 million or 0.24 per common share for the second quarter of 2016.

The decrease of operating expenses was offset by lower revenue. In addition, the result was affected by finance costs of 1.2 million in the second quarter of 2017, whereas finance income of 0.5 million was shown in the second quarter of 2016.

I will now turn the call back over to Adi for a summary of our two clinical programs and our pipeline. Adi?

Adi Hoess

Thanks a lot Florian. Our strategy is to maximize the value of our unencumbered clinical and preclinical pipeline of NK-cell and T-cell engagers, as well as from our platform. Were leveraging our lead product, AFM13, for CD30-positive lymphoma initially focusing on the Hodgkin Lymphoma salvage setting enabling a fast development path and allowing the establishment of a cost efficient marketing and sales structure.

In addition, we believe investigating AFM13, both as monotherapy and in combination with Keytruda, reduces its development. Overall, our preclinical and clinical strategy is designed from the scientific leadership of our NK-cell platform with CD16A as proprietary target. We are expanding the preclinical and clinical activities of our tetravalent and bispecific NK-cell engager platform in solid tumors with our preclinical candidate AFM24 and in hematologic diseases, where we intend to leverage additional opportunities for AFM13 and AFM26, for example, in combination with adoptive NK-cells. We also develop T-cell engagers and our lead T-cell engager, AFM11, is being investigated in two ongoing ALL and NHL trials. BMV564, a T-cell engager derived from our technology platform, is in clinical development through Amphivena to treat AML.

In addition, as mentioned earlier, moving beyond our standard format, we are developing different tetravalent bispecific antibody formats tailored to specific indications and patient populations. And as outlined in previous earnings calls, we have more projects ongoing at the discovery stage and preclinically, including molecules developed from our MHD type complex targeting platform.

Thank you very much for your interest. The call is now open for questions.

Question-and-Answer Session

Operator

Thank you. [Operator Instructions] Our first question now comes from Maury Raycroft from Jefferies. Please go ahead.

Maury Raycroft

Good morning. Thanks for taking my questions. So I was wondering if you can mention what the AFM13 dose was that the DLT patient received in the combo trial? And then what youre going to use in the expansion cohort? And then is this dose higher, lower or in line with your predictions?

Adi Hoess

Hi, Maury, this is Adi. What we have done is we have used or given a PD-1 as its active dose and have dosed up AFM13 under the following strategy, under the following regime. We always are initially giving AFM13 three times per week for two weeks. Then, we give AFM13 once weekly for six weeks and, subsequently, we dose AFM13 every three weeks. The starting dose was 0.15 mg/kg and then switching to 0.5 mg/kg, the next one was 0.5 mg/kg going to 1.5 mg/kg, and the highest dose was 3 mg/kg going then to 7 mg/kg. So the three is always three times per week, and the seven is the weekly or every three weeks. We have seen 1 DLT in the highest dose. So at three times 3 mg/kg and once 7 mg/kg then have included an additional three patients and have not observed another DLT. So thats why we decided to go with the highest dose of 3 mg/kg three times per week subsequently given and then subsequently followed by 7 mg/kg.

Maury Raycroft

Got it, okay. And you also mentioned earlier about the two PRs generated with the monotherapy treatment? And I think you said there is a stable disease, but I missed some of the additional context, and I was just wondering if you can recap that for me?

Adi Hoess

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Affimed Therapeutics' (AFMD) CEO Adi Hoess on Q2 2017 Results - Earnings Call Transcript - Seeking Alpha

Cellular Therapy – The World Leader in Stem Cell Technology

iPSCells Represent a Superior Approach

iPS cell-derived cardiomyocyte patch demonstrates spontaneous and synchronized contractions after 4 days in culture.

One of the greatest promises of human stem cells is to transform these early-stage cells into treatments for devastating diseases. Stem cells can potentially be used to repair damaged human tissues and to bioengineer transplantable human organs using various technologies, such as 3D printing. Using stem cells derived from another person (allogeneic transplantation) or from the patient (autologous transplantation), research efforts are underway to develop new therapies for historically difficult to treat conditions. In the past, adult stem and progenitor cells were used, but the differentiation of these cell types has proven to be difficult to control. Initial clinical trials using induced pluripotent stem (iPS) cells indicate that they are far superior for cellular therapy applications because they are better suited to scientific manipulation.

CDIs iPS cell-derived iCell and MyCell products are integral to the development of a range ofcell therapyapplications. A study using iCell Cardiomyocytesas part of a cardiac patch designed to treat heart failure is now underway. This tissue-engineered implantable patch mayemerge as apotential myocardial regeneration treatment.

Another study done with iPS cell-derived cells and kidney structures has marked an important first step towards regenerating, and eventually transplanting, a functioning human organ. In this work, iCell Endothelial Cellswere used to help to recapitulatethe blood supply of a laboratory-generated kidney scaffold. This type of outcome will be crucial for circulation and nutrient distribution in any rebuilt organ.

iCell Endothelial Cells revascularize kidney tissue. (Data courtesy of Dr. Jason Wertheim, Northwestern University)

CDI and its partners are leveraging iPS cell-derived human retinal pigment epithelial (RPE) cells to develop and manufacture autologous treatments for dry age-related macular degeneration (AMD). The mature RPE cells will be derivedfrom the patients own blood cells using CDIs MyCell process. Ifapproved by the FDA, this autologous cellular therapy wouldbe one of the first of its kind in the U.S.

Learn more about the technologybehind the development of these iPScell-derived cellular therapies.

Excerpt from:
Cellular Therapy - The World Leader in Stem Cell Technology

Ventolin proair – Rsv breathing treatments albuterol – Van Wert independent

Submitted information

OHIO CITY The Ohio City Park Association and the Lambert Days Committee has finalized plans for the 2017 festival.

Lambert Days is always the third full weekend in July. This years dates are July 21-23. This is also the 50th anniversary of Ohio Citys celebration of the life of John W. Lambert and his invention of Americas first automobile.

This years edition of Lambert Days will feature a communitywide garage sale. For more information, contact Laura Morgan at 419.965.2515. There will also be food all weekend in the newly renovated Community Building on Ohio 118.

Friday, July 21

Festivities start off with a steak dinner (carryout is available), starting at 4 p.m. Friday. Ohio Citys American LegionHarvey Lewis Post 346 will have aflag-raising ceremony at 5 Friday evening, while kids games and inflatables will also open at 5. At 6 p.m., the Lambert Days Wiffleball Homerun Derby will take place. For more information, contactLorenzo Frye 419.771.7037.

There will also be entertainment at 6 p.m. featuring Cass Blue. At 7, there will be a adult Wiffleball tournament. For more information, contact Brian Bassett419.203.8203. A Texas Hold em Tournament will begin at 7 p.m. Friday, along with Monte Carlo Night, which begins at 8 p.m. For more information, contact Jeff Agler at 419.513.0580.

Entertainment for Friday night starts at 8 and will be the band Colt & Crew. There will also be a fireworks display at 10:15 p.m. Friday (Saturday night is the rain date).

Saturday, July 22

Saturday morning begins with a softball tournament at 8. For more information, contact Brian Bassettat 419.203.8203. There will also be a coed volleyball tournament that starts at 9 a.m. Saturday. For more information, contact Tim Matthews at 419.203.2976. The Lambert Days Kids Wiffleball Tournament starts at 10 a.m. Saturday. For more information, contact Lorenzo Frye at 419.771.7037.

Kids games and Inflatables continue at 11 Saturday morning. Cornhole tournament registration and 3-on-3 basketball tournament registration start at noon, while both tournaments begin at 1 p.m. For more information on cornhole, contact Josh Agler at 567.259.9941 and for 3-on-3 basketball, contact Scott Bigham at 419.953.9511.

The Hog Roast Dinner starts at 4 p.m. Saturday and carryout is available. There will also be music under the tent by Jeff Unterbrink at 4. Bingo will start at 5 p.m., and the night ends with entertainment by Megan White and Cadillac Ranch.

(more)

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Ventolin proair - Rsv breathing treatments albuterol - Van Wert independent

Proventil hfa ventolin hfa – Proventil inhaler dosage for adults – Longboat Key News

Major Headlines

11:55 am | These guests basically utilize the beach at night as their own personal entertainment venue....

09:54 am | At the pinnacle of Longboat luxury properties stands the Ohana Estate priced at $19.9 million....

09:45 am | The building provides a base of operations for collaborating scientists from around the world....

01:05 am | Officer says video taping of the suspects apparently angered them, causing the incident to intensify....

01:00 am | Mr. Mayor, I think you are totally out of order. This has not been noticed, said Spoll....

12:55 am | There have been 46 commission races for seats in the five town districts since 2000. Of those, 72 percent, or 33 of them, having only a single...

12:51 am | Town Manager Dave Bullock found the next Public Works Director for Longboat Key close to home....

12:02 am | Rotary Club honors those who protect and serve our island as residents and families show support....

11:51 pm | More stringent ordinance enacted due to LBK having highest number of disorientations in area....

11:48 pm | The Unstoppable Wasp is about females in science working together for a common cause....

11:31 pm | There is no better place Ive run across where residents are as smart, rationally informed and care so much about where they live....

11:28 pm | Im not sure weve thought through the ramifications, said Commissioner Randy Clair....

11:25 pm | Mote Marine Laboratory documented the first three local sea turtle nests of 2017 two on Sunday, April 30, and one on Monday, May 1 in Venice,...

01:58 pm | The stakes could not be higher. The future look of the island, the evolution of property values and the protection of development rights all intersect. ...

01:54 pm | Mote tags 34 sharks in mission to understand habitat, patterns and populations....

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Proventil hfa ventolin hfa - Proventil inhaler dosage for adults - Longboat Key News

The Gilmer Mirror – Hurray for Gurdon and Yamanaka Nobel Prize … – Gilmer Mirror

The research studies carried out by John B. Gurdon (Anglo-Saxon) and Shinya Yamanaka (Japanese) were awarded the Nobel Prize in Medicine. These two scientists are considered of being the fathers of cellular reprogramming. They have achieved to create cells that behave identically to embryonic cells, however, without having to destroy human embryos. The Swiss Academy declared that both Gurdon and Yamanaka have revolutionized the current knowledge of how cells and organisms are developed, which has led to the perfection of the absurd methods of diagnosis and therapy.

Jhon Bertrand Gurdon, professor of the Zoology Department of the University of Cambridge, admitted of feeling extremely honored for such a spectacular privilege.

Moreover, Shinya Yamanaka discovered the so called induced pluripotent stem cells (iPS), which have the same proprieties of the embryonic ones and are able to turn into whatever other type of body cell. He asserted that he will continue to conduct research in order to contribute to society and medicine. For him that is a duty.

Yamanaka created four types of genes that supply cells with their pluripotentiality, in other words, the same capacity that embryonic stem cells have. If implanted in differentiated cells, for example of skin, they become pluripotent stem cells. The iPS supply a vast amount of plasticity just as embryonic stem cells do, however, without requiring the extermination or cloning of human embryos, since the initial cells can be obtained from the same patient. In this aspect, these cells have the same status as adult stem cells do, with the advantage of their versatility.

The dilema that has been stirred by the iPS is being resolved due to recent studies carried out by Leisuke Kaji (Universidad de Edimburgo) and Andreas Nagy (Samuel Lunenfeld Research Institute of Mount Sinai Hospital of Toronto).

The created iPS perennially retain their pluripotentiality. There is still the need of research to be conducted concerning the control of the difference between these cells in order for them to create the tissue that is necessary for each case. As Kaji affirms in The Guardian, it is a step towards the practical use of reprogrammed cells in the field of medicine, which could eventually lead to eliminating the need of counting on human embryos as the main source of stem cells.

The Episcopal Subcommittee for the Family and Defense of Life of the Episcopal Conference, beliefs that no Catholic could support practices such as abortion, euthanasia or the production, freezing and/or manipulation of human embryos.

Clement Ferrer

Independent Forum of Opinion

http://indeforum.wordpress.com/

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The Gilmer Mirror - Hurray for Gurdon and Yamanaka Nobel Prize ... - Gilmer Mirror

Stem cells: JP2MRI, CET discover safer, more ethical biotechnology – Sioux City Catholic Globe

By RENEE WEBB rwebb@catholicglobe.org

As the use of stem cell research and therapy continues to expand, one medical research institute located in Iowa strives to uphold Catholic teachings in bioethics.

The John Paul II Medical Research Institute (JP2MRI), a non-profit of Iowa City, was founded by Dr. Alan Moy in 2007 to address a shortcoming when it came to pro-life values being upheld concerning a variety of medical practices and issues. The doctor also is co-founder and CEO of Cellular Engineering Technologies (CET), a for-profit biotechnology company that manufactures commercial adult stem cells and other biotechnology products.

He explained that JP2MRI was founded a year after starting CET to advance the application of adult stem technology to clinical applications in the area of neurodegenerative disease, rare disease, cancer and chronic diseases of unmet needs or in underperformed diseased areas. His concern was that the United States was falling behind other countries in the area of adult stem cell research.

Recently, through collaborative research by JP2MRI and CET, a new method for creating safer induced pluripotent stem cells, or iPSC, for clinical use was discovered.

We started work in traditional adult stem cells over a decade ago, Moy explained. The controversy was that among the secular scientific community, adult stem cells were viewed as inferior to embryonic stem cells because they could not convert or differentiate into the variety of cells that embryonic stem cells could.

When iPSC technology was discovered by a Japanese Nobel laureate scientist about 10 years ago, it was an ethical alternative to embryonic stem cells. iPSC are noncontroversial adult stem cells that are genetically reprogrammed into embryonic-like stem cells without using human embryos.

But that technology had inherent safety issues just like embryonic stem cells. Most embryonic stem cells and iPS cells have the risk of causing tumors because of their genetic instability, Moy said. What we worked on was trying to reduce the tumor risk.

Building on the original iPSC technology, JP2MRI and CET developed a method by using a variety of chemicals to replace known cancer-causing genes in the process.

Now we have an iPS technology that is safer, said Moy, who noted an added benefit is potential reduced cost in drug development.

Potential applications

He spoke about practical applications of this technology such as expanding the use of stored cord blood stem cells for future medical treatment if a disease develops in the child.

We have a means where we can take the cord blood and make an iPS cell which can have lifelong utility and diversity, Moy added.

For those who do not have stored cord blood, he said all is not lost as blood can be drawn and stored for people to create their own iPS cell for future use.

This technology can also provide a viable alternative to embryonic stem cells and aborted fetal tissue that are currently used by the pharmaceutical industry, noted Moy, to produce vaccines, gene therapy, cell therapy and protein therapeutics.

Right now with protein manufacturing, half of it is done using animal cells to produce human proteins, he explained. The problem is some of the human proteins that are produced have some minor animal characteristics and they are not entirely human so there is a push to produce purely human proteins out of human cells. Unfortunately, the vast majority of human cell lines used in protein manufacturing or in vaccine development are derived from aborted fetal tissue.

Moy anticipates there will increasingly be a movement to shift toward human cell manufacturing, and if we dont come up with non-controversial human cells, we are going to have a lot of controversial human protein therapeutics, gene therapies and vaccines that will be distributed at hospitals that must be administered by doctors.

Morals and ethics

This can create moral and ethical problems. Catholic hospitals and/or Catholic doctors will be forced to decide if they will use that type of product made with illicit cells.

We have to have alternative products that are equal or better than the products that are currently out there, said Moy.

The Catholic Church, as well as the average person, may not always be aware of the unethical nature of many of these products. Moy said he has been trying to communicate areas of concern to the Catholic community for years.

The evolution of biotechnology over decades has become secularized and the power is in the secularists, he said. Advancement of illicit-cell treatment and therapy is a serious potential threat to the Catholic health care system including Catholic hospitals and Catholics who are healthcare providers.

Moy feels strongly about Catholics and the church being pro-active in the bioethics arena.

The only way in which we can influence the biotechnology field is through innovation, he said. Through innovation, if you produce something they want that has technical advantage, then one can influence the direction of biotechnology. Pro-life individuals need to move from a passive bystander to an activist role.

That is part of the reason he founded the JP2MRI, which is grounded in a pro-life bioethics that respects the dignity of every human life. While more than 300 non-profit institutes and organizations engage in and support human embryonic stem cell research, JP2MRI seeks to find cures and therapies exclusively using a variety of adult stem cells and specifically the iPSC, which are derived from adult cells.

Moy said they are not only looking for ways to produce a variety of products using the safer iPS cells, but plan to license them so other scientists, companies and industries can take advantage of these cells to pursue more ethical biotechnology.

Here is the original post:
Stem cells: JP2MRI, CET discover safer, more ethical biotechnology - Sioux City Catholic Globe

Hurray for Gurdon and Yamanaka, Nobel Prize Winners for Pro-life Medicine – Gilmer Mirror

The research studies carried out by John B. Gurdon (Anglo-Saxon) and Shinya Yamanaka (Japanese) were awarded the Nobel Prize in Medicine. These two scientists are considered of being the fathers of cellular reprogramming. They have achieved to create cells that behave identically to embryonic cells, however, without having to destroy human embryos. The Swiss Academy declared that both Gurdon and Yamanaka have revolutionized the current knowledge of how cells and organisms are developed, which has led to the perfection of the absurd methods of diagnosis and therapy.

Jhon Bertrand Gurdon, professor of the Zoology Department of the University of Cambridge, admitted of feeling extremely honored for such a spectacular privilege.

Moreover, Shinya Yamanaka discovered the so called induced pluripotent stem cells (iPS), which have the same proprieties of the embryonic ones and are able to turn into whatever other type of body cell. He asserted that he will continue to conduct research in order to contribute to society and medicine. For him that is a duty.

Yamanaka created four types of genes that supply cells with their pluripotentiality, in other words, the same capacity that embryonic stem cells have. If implanted in differentiated cells, for example of skin, they become pluripotent stem cells. The iPS supply a vast amount of plasticity just as embryonic stem cells do, however, without requiring the extermination or cloning of human embryos, since the initial cells can be obtained from the same patient. In this aspect, these cells have the same status as adult stem cells do, with the advantage of their versatility.

The dilema that has been stirred by the iPS is being resolved due to recent studies carried out by Leisuke Kaji (Universidad de Edimburgo) and Andreas Nagy (Samuel Lunenfeld Research Institute of Mount Sinai Hospital of Toronto).

The created iPS perennially retain their pluripotentiality. There is still the need of research to be conducted concerning the control of the difference between these cells in order for them to create the tissue that is necessary for each case. As Kaji affirms in The Guardian, it is a step towards the practical use of reprogrammed cells in the field of medicine, which could eventually lead to eliminating the need of counting on human embryos as the main source of stem cells.

The Episcopal Subcommittee for the Family and Defense of Life of the Episcopal Conference, beliefs that no Catholic could support practices such as abortion, euthanasia or the production, freezing and/or manipulation of human embryos.

Clement Ferrer

Independent Forum of Opinion

http://indeforum.wordpress.com/

See the article here:
Hurray for Gurdon and Yamanaka, Nobel Prize Winners for Pro-life Medicine - Gilmer Mirror

Novel Findings Obtained with the PURE EP System to be Presented at American Heart Association’s BCVS Scientific … – Cardiovascular Business

Minneapolis, MN, June 26, 2017 (GLOBE NEWSWIRE) -- BioSig Technologies, Inc.(OTCQB:BSGM), a medical device company developing a proprietary platform designed to address an unmet technology need for the $4+ billion electrophysiology (EP) marketplace, today announced that the American Heart Associations 13thAnnualBasic Cardiovascular Sciences (BCVS) 2017 Scientific Sessions: Pathways to Cardiovascular Therapeuticshas accepted two abstracts for presentation that feature novel preclinical findings with BioSigs PURE EP System. The conference will be held July 10-13 in Portland, Oregon and includes the next best thing in cardiovascular research.

The abstracts, entitled, Use of a Novel Electrogram Filter to Visualize the Conduction Tissue Signals in the Ventricle in Sinus Rhythm and Arrhythmia: Canine Studies and "Assessment of Catheter Position Above or Below the Aortic Valve by Evaluation of Characteristics of the Electrogram: An Acute Canine Study", werewritten in collaboration with electrophysiologists from Mayo Clinic and will be presented during scientific poster sessions from 4:30pm 7pm on July 10 and 12, respectively.

BioSig is extremely pleased to have two abstracts, featuring our PURE EP System, accepted into the Basic Cardiovascular Sciences Conference sponsored by the American Heart Association, stated Mr. Ken Londoner, Chief Executive Officer and Chairman of BioSig Technologies. Our collaboration with Mayo Clinic physicians has resulted in seven publications to date featuring BioSigs platform technology. And, we intend to strive towards improving visualization of cardiac signal information during EP procedures to help bring benefits to those patients who suffer with, and doctors who treat, arrhythmia.

About the Basic Cardiovascular Sciences Conference

The 13th Annual BCVS 2017 Scientific Sessions: Pathways to Cardiovascular Therapeutics has become the premier conference for molecular cardiovascular biology and disease. Sponsored by the American Heart Association Basic Cardiovascular Sciences Council, the worlds leading organization of cardiovascular scientists, this conference strives to improve basic cardiovascular regulation through new therapies and insights in cardiovascular disease, as well as research in fields like microRNAs, cardiac gene and cell therapy, cardiac development, as well as tissue engineering and iPS cells.

BCVS 2017 convenes basic and translational cardiovascular scientists from around the world with the common goal to discover pathways to cardiovascular therapeutics and promoting cardiovascular health. This meeting has become the go to meeting for intra- and interdisciplinary cross-fertilization of ideas and incorporation of new approaches from the general scientific community and plays a pivotal role in the training of junior scientists and trainees. The program includes a diversity of speakers representing the best cardiovascular scientists from around the world.

About BioSig Technologies

BioSig Technologies is a medical device company developing a proprietary technology platform designed to improve the $4+ billion electrophysiology (EP) marketplace ( http://www.biosigtech.com). Led by a proven management team and a veteran, independent Board of Directors, Minneapolis-based BioSig Technologies is preparing to commercialize its PURE EP(TM) System. The technology has been developed to address an unmet need in a large and growing market.

The PURE EP System is a novel cardiac signal acquisition and display system which is engineered to assist electrophysiologists in clinical decision making during procedures to diagnose and treat patients with abnormal heart rates and rhythms. BioSigs main goal is to deliver technology to improve upon catheter ablation treatments for prevalent and deadly arrhythmias. BioSig has partnered with Minnetronix on technology development and is working toward FDA 510(k) clearance and CE Mark for the PURE EP System.

Forward-looking Statements

This press release contains forward-looking statements. Such statements may be preceded by the words intends, may, will, plans, expects, anticipates, projects, predicts, estimates, aims, believes, hopes, potential or similar words. Forward-looking statements are not guarantees of future performance, are based on certain assumptions and are subject to various known and unknown risks and uncertainties, many of which are beyond the Companys control, and cannot be predicted or quantified

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Novel Findings Obtained with the PURE EP System to be Presented at American Heart Association's BCVS Scientific ... - Cardiovascular Business

Intranasal ipratropium in the treatment of vasomotor rhinitis – Queens Tribune


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Cipro false positive drug test – Queens Tribune


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Stem cells: the future of medicine – Medical Xpress

June 23, 2017

Imagine being able to take cells from your skin, transform them into other types of cells, such as lung, brain, heart or muscle cells, and use those to cure your ailments, from diabetes to heart disease or macular degeneration. To realise this, however, challenges still remain, Professor Janet Rossant, a pioneer in the field, says.

All across the world, scientists have begun clinical trials to try and do just that, by making use of the incredible power and versatility of stem cells, which are special cells that can make endless copies of themselves and transform into every other type of cell.

While human embryos contain embryonic stem cells, which help them to develop, the use of those cells has been controversial. The scientists are using induced pluripotent stem cells instead, which are other cells that have been reprogrammed to behave like stem cells.

"There are still significant challenges that we need to overcome, but in the long run we might even be able to create organs from stem cells taken from patients. That would enable rejection-free transplants," said Professor Janet Rossant, a pioneer in the field.

The mouse that changed everything

A speaker at the recent Commonwealth Science Conference 2017 held in Singapore and organised by Britain's Royal Society and Singapore's National Research Foundation, Prof Rossant gave an overview of stem cells' origins, history, uses and potential.

Now a senior scientist at The Hospital for Sick Children (also known as Sick Kids) in Toronto, Canada, after a decade as its chief of research, she was the first scientist to demonstrate the full power of stem cells in mice.

In the early 1990s, scientists believed that stem cells could only become certain types of cells and carry out limited functions. Based on her own research and that of others, however, Prof Rossant believed that they were capable of far more.

Working with other scientists, she created an entire mouse out of stem cells in 1992, upending the conventional wisdom. "We went on to create many baby mice that were completely normal, and completely derived from stem cells grown in a petri dish," she said.

"That was an amazing experiment, and it was instrumental in making people believe that human embryonic stem cells could have the full potential to make every cell type in the body," she added.

When scientists learned how to remove stem cells from human embryos in 1998, however, controversy ensued. Many lobbied against the cells' use in medical research and treatment due to the moral implications of destroying even unwanted embryos to gain the cells.

In Canada, Prof Rossant chaired the working group of the Canadian Institutes of Health Research on Stem Cell Research, establishing guidelines for the field. These guidelines helped to keep the field alive in Canada, and were influential well beyond the country's borders.

In 2006, Japanese researchers succeeded in taking skin cells from adult mice and reprogramming them to behave like embryonic stem cells. These revolutionary, induced pluripotent stem (IPS) cells allowed scientists to sidestep the ongoing controversy.

The challenges in the way

While stem cells have been used for medical treatment in some cases bone marrow transplants, for example, are a form of stem cell therapy there are several challenges that need to be overcome before they can be used more widely to treat diseases and injuries.

"We need to get better at turning stem cells into the fully mature cells that you need for therapy. That's going to take more work. Another issue is that of scale-up. If you're going to treat a patient, you need to be able to grow millions of cells," said Prof Rossant.

She added: "Safety is another concern. One of the most exciting things about pluripotent stem cells is that they can divide indefinitely in the culture dish. But that's also one of the most scary things about them, because that's also how cancer works.

"Furthermore, because we need to genetically manipulate cells to get IPS cells, it's very hard to know whether we've got completely normal cells at the end of the day. These are all issues that need to be resolved."

She noted that some scientists are working on making "failsafe" IPS cells, which have a built-in self-destruct option if they become dangerous. "Bringing stem cells into regenerative medicine is going to require interdisciplinary, international collaboration," she said.

In the meantime, stem cells have been a boon to medical research, as scientists can use them to create an endless supply of different cells to study diseases and injuries, and test drugs. "That's the biggest use of IPS cells right now," Prof Rossant said.

Sick kids and how to help them

At SickKids, which is Canada's largest paediatric research hospital, she has been using stem cells to study cystic fibrosis, a frequently fatal genetic disorder that causes mucus to build up and clog some organs such as the lungs. It affects primarily children and young adults.

SickKids discovered the CFTR gene that, when mutated, causes the disease. It was also the first to produce mature lung cells, from stem cells, that can be used to study the disease and test drugs against it.

Even better, Prof Rossant and her team were able to turn skin cells from cystic fibrosis patients into IPS cells and then into lung cells with the genetic mutation specific to each of them. This is critical to personalising treatment for each patient.

"Drugs for cystic fibrosis are extraordinarily expensive, and patients can have the same mutation and yet respond differently to the same drug," Prof Rossant explained. "With our work, we can make sure that each patient gets the right drug at the right time."

In 1998, Prof Rossant also discovered a new type of stem cell in mice, now called the trophoblast stem cell. These surround an embryo and attach it to the uterine wall, eventually becoming the placenta. She is using such cells to study placenta defects and pregnancy problems.

By using IPS cells to create heart cells and other cells, pharmaceutical companies can also test their new drugs' effectiveness and uncover potential side effects, as well as develop personalised medicines.

"There are still huge amounts of opportunities in pluripotent stem cells," said Prof Rossant, who has won numerous awards for her research, including the Companion of the Order of Canada and the 2016 Friesen International Prize in Health Research.

She is also president and scientific director of the Toronto-based Gairdner Foundation, which recognises outstanding biomedical research worldwide, and a professor at the University of Toronto's molecular genetics, obstetrics and gynaecology departments.

"Meetings like the Commonwealth Science Conference are a fantastic opportunity for scientists to come together, learn about each other's work and establish new relationships, which will help to push science forward, including in stem cell research," she said.

She noted: "The world of science is becoming increasingly interdisciplinary, so this kind of meeting of minds across nations, cultures and scientific fields is really the way of the future."

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Probing Psychoses – Harvard Magazine

Andrew LeClerc knew something was wrong when he heard voices when no one else was around. Some were those of people he knew, others were unfamiliar, but all had the authentic mannerisms of real people, not his imagination. He was in his early twenties, unsure of his direction in life, and had been taking synthetic marijuana to ease stress from past traumas. Disturbed by the voices, he sought help in an emergency room and voluntarily admitted himself to a psychiatric hospital, not realizing he would be kept there for six days. He was diagnosed with psychosis, but had little interaction with a therapist. You mostly sit around with coloring books, he says. It felt like a punishment, when all he wanted was help.

Afterward, he contacted therapists, but many were booked. An online search led him to a research study at Beth Israel Deaconess Medical Center in Boston for people newly diagnosed with psychotic disorders. In January 2014, he entered a two-year study that compared two approaches to psychotherapy to help manage cognitive impairments and other symptoms. He was also prescribed an antipsychotic medication.

Eventually he was diagnosed with schizophrenia. Now, about four years later, at 26, LeClerc is learning to live with the condition. Its hard for a person whos diagnosed with schizophrenia to be told somethings not real when they think its real, he says. He continues to take antipsychotic medications that help control his hallucinations and lives in an apartment below his parents in Middleton, Massachusetts. Hes hoping to start a small business, putting his love of gardening to work as a landscaper.

But more importantly, hes learned to make peace with his mind. He likes to say: I dont hear voices, I hear my own brain. When voices do appear, he recognizes them as a product of an aberrant auditory cortex, and he thinks about engaging his prefrontal cortexthe decision-making part of the brainto help him distinguish fact from fiction. I have tools to pull myself back to the moment, he says.

Not everyone who struggles with schizophrenia is able to find such stability. The illness takes many forms; symptoms may include hallucinations and delusions, lack of motivation, and cognitive problems similar to dementia. It tends to strike in the late teens and early twenties, robbing young people of their mental stability just as theyre entering adulthood, beginning careers, or pursuing a college degree. Some improve, while others experience a long mental decline.

The treatments that we have are useful but not great, says Matcheri Keshavan, Cobb professor of psychiatry at Harvard Medical School (HMS) and the leader of the study that LeClerc participated in. The medications used to treat schizophrenia are decades old, and only ameliorate symptoms. Like other psychiatric illnesses, schizophrenia has suffered from a lack of investment from pharmaceutical companies. Says Keshavan, We need better medications that really address the underlying cause of this illness.

But those causes are still mysterious. What scientists do know is that schizophrenia tends to run in families. About 70 percent to 80 percent of a persons risk of developing the illness, Keshavan says, can be explained by genetic factors. Recently, theres been a surge of effort to capitalize on that fact. Advances in genetics have made it possible to search not only for clues about schizophrenia and other psychiatric illnesses hidden within thousands of human genomesbut also for potential new treatments.

As a result, theres been a renaissance in research on schizophrenia and other psychiatric disorders, and some cautious optimism. Its been possible to make real if still early progress in understanding what genes and molecules influence these illnesses, says Steven McCarroll, Flier associate professor of biomedical science and genetics. At Harvard, the leading force is the Stanley Center for Psychiatric Disease Research at the Broad Institute, which is pouring new funding and resources into amassing data on the genetics of mental illness.

Bringing the power of genomics to psychiatric disease fulfills a long-held goal for the Stanley Centers director, Steven Hyman, professor of stem cell and regenerative biology. An HMS professor of psychiatry before becoming head of the National Institute of Mental Health (NIMH) in 1996, Hyman was frustrated by the sluggish progress on the science of psychiatric disorders, as research on illnesses like cancer, heart disease, and diabetes marched ahead. Schizophrenia in particular is challenging to study because its uniquely human. Scientists can study limited aspects of psychiatric illness in animals if they can measure an observable behavior, such as avoiding social interactions or grooming excessively. But psychosis is a problem of thinking; animals, as far as is known, dont experience it in any way we can measure. Its also challenging because brain tissue is so inaccessible. We were really hampered, Hyman says, and I, frankly, didnt know all that much more when I was at NIMH in the late 1990s than careful observers knew at the turn of the twentieth century.

Steven Hyman, director of the Stanley Center for Psychiatric Disease Research Photograph by Stu Rosner

When he left the position, Hyman was interested in researching psychiatric disease but didnt see a rigorous path to do so; instead, he accepted a position as Harvards provosttaking what he now refers to as a 10-year timeout. During that time, a revolution occurred. Genetic technologies and vastly expanded computer power opened new paths for studying the biological basis of complex diseases.

The Broad Institute launched the Stanley Center in 2007 under inaugural director Edward Scolnick, thanks to an initial $100 million in private funding from philanthropists Ted and Vada Stanley, aiming to bring much-needed innovation to treatments for psychiatric disease by harnessing the power of genomics. (The Stanleys provided another $650 million in 2014, an unprecedented gift for psychiatric research.) Partly as a result, the center has gathered the worlds largest collection of DNA samples for studying not only psychiatric diseasesincluding schizophrenia, autism, ADHD, and bipolar disorderbut also healthy control subjects. The resulting data are freely available to the public.

The human genome has started to give us a really powerful way into the problem, Steven McCarroll explains, because the key source of scientific leverage that we have is we know that schizophrenia and other psychiatric illnesses are heritablethey aggregate in families. Their molecular secrets are almost certainly hidden in the way our genomes vary from person to person.

Much of the research on genetics and disease has focused on what McCarroll calls genetic sledgehammersgenes that when mutated would almost certainly make you sick. But schizophrenia, like most common diseases, is genetically complex. The hereditary component of the disease may be a product of tens to hundreds of genetic nudges, variations that dont cause disease by themselves, but together make people vulnerable to illness.

Studying genetic nudges requires amassing large numbers of DNA samples to achieve the statistical power to find subtle variations that may contribute to disease, a project thats taken enormous collaborative effort by many scientists and institutions around the world. The Psychiatric Genomics Consortiumthe largest scientific collaboration involving psychiatric diseaseformed in 2007 and comprises hundreds of investigators in 38 countries and nearly a million genetic samples. The Stanley Center has served as the hub for data sharing, aggregation, and analysis to further the consortiums discoveries.

One of the key tools for uncovering the genetic basis of disease is the genome-wide association study (GWAS)a way of quickly sorting through the common variations in genomes to find those that are more common in people with a given trait or disease than in those without. Associate professor of medicine Mark Daly, who leads the analytic hub of the consortium, says that scientists originally thought such studies might uncover a handful or two of DNA variants that could be statistically correlated with schizophrenia. But rather than identifying a few standouts, the consortiums Schizophrenia Working Group found a crowd of genetic associations, each contributing just a tiny amount of risk. A landmark paper published in 2014 in the journal Nature, led by Michael ODonovan of Cardiff University, described 108 different locations in the genome that harbored variants associated with schizophrenia.

GWAS studies can identify only stretches of DNA: like flags on a zoomed-out map of a city, they provide a neighborhood, not the exact address. We know where the variants are, one of which is likely to be the causal variant, but cant say for sure which one, says assistant professor of medicine Ben Neale, who is developing methods to analyze genomic data. Another approach is to sift through genomes in finer-grained detail by directly reading each letter of the DNA sequence. Such work is time-consuming, but it can help uncover rare genetic differences that are linked to disease, many of which have a stronger effect than common variants. Work by the consortium has also analyzed areas of DNA that are deleted or duplicated, called copy number variations. People with schizophrenia tend to have more such variations overall, and the genes they affect can provide clues to the diseases origins.

Meanwhile, the Stanley Center and other institutions are working to collect thousands more DNA samples from people with schizophrenia and other psychiatric disorders, hoping to identify even more genetic associations of risk. Hyman doesnt see such data-gathering as an endless project. We should kill this problem, he says, meaning in some reasonable number of yearsseven to 10we should have proceeded so far in the genetics of schizophrenia, bipolar disorders, autism, perhaps some other disorders, that weve reached diminishing returns in terms of biological information.

But so far, the picture is still incomplete. The vast majority of genetic samples, for instance, come from people of European ancestry. From a purely scientific point of view, it means were missing a large proportion of the worlds genetic diversity, says Karesten Koenen, professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health. Most of that diversity is in Africa: There is much more diversity in African genomes than in those of people from other parts of the world.

Koenen is leading an effort through the Stanley Center to launch genetic research on psychiatric disease in Ethiopia, Uganda, Kenya, and South Africa. Their researchers are partnering with researchers and academic and clinical institutions in those countries and will be gathering DNA samples and clinical information from people diagnosed with schizophrenia. We really want to build local capacity, she says, and develop sustainable research programs that can be led by local scientists and clinicians. The center also plans to extend the effort to Latin America, beginning in Mexico.

This effort will help fill in the genetic picture of psychiatric illness, and will also help correct a vast imbalance. Geneticists are beginning to use data to classify patients based on their risk of developing complex diseases, including schizophrenia. But these risk profiles, Koenen says, lose accuracy when applied to people of African descent. As this kind of profiling makes its way into medicine, she says, Theres a risk that if we dont extend this research to Africa, the health disparity and treatment gap will widen.

What will all this data amount to? Theres a misconception, McCarroll says, that the goal of this research is to conjure up a crystal ball genetic test that will give people personalized treatments based on their unique portfolio of genes. Thats not the aim. Our goal, he says, is to understand the core biological processes in the illnesses, so that innovative treatments can be developed that can treat anyone. Scientists hope that the dizzying array of schizophrenia-related genes will converge onto a few basic processes in the brain, once the function of those genes is understood.

But even as scientists have made dramatic leaps in discovering genetic risk factors of complex diseases, the task of understanding how those genes work is a different, and slower, task.

Researchers from Harvard and the Broad Institute have grown human brain organoids, three-dimensional organ models cultured from stem cells, to study the genetics of psychiatric illness. This series shows (clockwise from upper left) growth at 1, 3, 6, and 9 months, with development of synapses indicated in green. Quadrato et al./Nature 2017

McCarroll was lead author of a study making one of the strongest links between a specific genetic variant and its role in schizophrenia. Working with Aswin Sekar (then a graduate student, now a research fellow), he focused on the most powerful signal of risk in GWAS studies to date, a stretch of DNA in chromosome 6 that was known to harbor many genes involved in the immune system. They focused on one called C4, which has a high degree of variability in humans: each of its different forms may be present in multiple copies in one individual. By using both genetic data and postmortem brain tissue, they found that people with schizophrenia are more likely to have variants of the C4 gene that lead to higher levels of one gene product, C4A, in brain cells.

C4A is one of several proteins involved in a type of immunity called the complement pathway, which helps clear damaged cells and harmful microbes from the body. As part of their study, McCarroll and Sekar collaborated with associate professor of neurology Beth Stevens, whose previous research with mice clarified an ingenious connection between the complement pathway and the brain. Scientists know that as the brain develops, it churns out new cells, which form billions of connections called synapses. In adolescence and early adulthood, some of these connections are pared back, a process called synaptic pruning. In mice, Stevens has found, this pruning is mediated by the complement pathway, which triggers immune cells called microglia to attack neural connections: literally nibbling at synapses.

Sekar, McCarroll, and Stevens also worked with professor of pediatrics Michael Carroll, who had developed mice with varying copies of the C4 gene, and showed that too much C4 activity in the animals can lead to excess pruning. Its too much of a good thing, Stevens says. Their finding suggests that schizophrenia, in some cases, may be caused by loss of synapses in adolescencean especially promising result because it supports clinical observations: synaptic pruning coincides with the age when schizophrenia typically emerges, and brain imaging shows that many people with schizophrenia experience a thinning of the prefrontal cortex in the early stages of disease.

Steven McCarroll, Flier associate professor of biomedical science and genetics Photograph by Stu Rosner

McCarroll emphasizes that the C4A variation contributes only a small amount of risk of disease, but may collude with other variants to tip the brain past a threshold. There are a lot of genetic findings that map to synapses, says Hyman, so some of those other variants may contribute to a larger disruption in how synapses are formed and maintained. But other processes are likely at work in schizophrenia as well. Some genetic risk variants relate to a chemical signal in the brain called glutamate, and others to ion channels, proteins that determine how electrical signals propagate in brain cells. There are also others, Hyman adds, that, frankly, just have us scratching our heads.

The work on C4 offers an example of how genetics is beginning to help neuroscience move forward. Its opened up a ton of new directions and strategies for our group, says Stevens. Across Harvard and the Stanley Center, a growing community is launching collaborative projects with the goal of taking psychiatric disease research into new territories.

One priority is developing new models for teasing out the role of genes in the brain. Scientists have been able to study some behaviors that relate to mental illness in animals, but there is no animal model for schizophrenia. Michael Carroll is now working to extend the C4 study by creating humanized mice that carry human C4 genes, which may make it possible to study their function in a living brain.

Other researchers are trying to develop new ways to study psychiatric disease in humans. Paola Arlotta, professor of stem cell and regenerative biology, explains that when scientists are able to get samples of human brain tissuefrom patients undergoing surgery, postmortem donations, or even tissue from fetusesthe cells die quickly. They cant be propagated and studied in a laboratory, so there is no renewable source of the actual endogenous tissue.

Stem cells have emerged as a way around that problem. Scientists can now take cells from the skin or hair and transform them into induced pluripotent stem (iPS) cells that are capable of becoming other cell types, including brain cells. (At the Stanley Center, Arlotta and other scientists are exploring how to transform iPS cells into specific types of brain cells.) The iPS cells allow scientists to study how cells derived from a person of one genetic background differ from those of another person. Scientists can also use the genome-editing tool CRISPR-Cas9 to introduce specific genetic changes and study their effects.

But theres very little that can be learned about psychiatric disease from isolated cells: brain activity depends on the constant chatter of many cells that are intricately connected. Arlotta has been investigating whether neural stem cells can be spun into something that behaves more like human brain tissue. So-called organoidsclusters of millions of cells up to a few millimeters in diametercan be formed from growing stem cells in a nutrient-rich solution. Organoids have already been used to study events that happen in early development: last year, a team of researchers used them to study the effects of the Zika virus on developing brains.

But since psychiatric diseases like schizophrenia emerge later in life, Arlotta wants to make organoids grow larger and live longer, and to understand whether they can mimic some of the properties of an older brain. This is a new tissue were making, she says, and so the questions that we want to answer are: can we develop them for a very long time, can we understand the cellular composition, can we see if these organoids make actual networks and communicate with each other?

To better characterize these cell-based models, Arlotta and her colleague Kevin Eggan, a fellow professor of stem cell and regenerative biology, are collaborating with McCarroll to apply a technology his lab developedDropSeqthat makes it possible to analyze gene activity in individual cells. The technology will provide a detailed, cell-by-cell understanding of what these models may reveal. In a Nature paper published in April, Arlottas team demonstrated that its possible to cultivate human brain organoids for nine months or more. Analysis revealed that the organoids are filled with a diverse mix of brain-cell types, and that these cells actually form interconnected networks, suggesting they may begin to function in ways that brains do.

But how much meaningful information about psychiatric disorders can be gleaned by studying individual cells or clusters of artificial tissue remains unclear. And an even bigger question is how to use these models to study the effects of genetic nudges. Disease genetics, typically, has been studied by altering or removing genes, one at a time, in an animal. Studying a whole suite of subtle genetic variations in a model system is a completely new idea.

There is no playbook, says Hyman. He acknowledges that the work is risky; many of these projects are possible only because the Stanley Centers open-ended funding makes it easier for labs to work together to pursue new ideas. We spend many tens of millions of dollars a year, and were accountable only at the end of the year to our scientific advisory board, and we tell them our strategy, he says. It gives us enormous flexibility, but its an enormous responsibility.

Some scientists and clinicians believe that gathering genetic data and studying cells is a misguided strategy for alleviating psychiatric illness. They see it as reductionist, and argue that it emphasizes the inborn biological origins of illnesses rather than other factorslike abuse, trauma, drug use, and emotional stressthat are known to play a role in their development. Hyman answers, Genes are not fate, but genes have an awful lot to say. Genetics and the environment both undoubtedly contribute to disease, but both ultimately must act on the brainand genetics happens to be a more tractable way to study whats happening in the brain.

Genetics is already providing insights that could help alter the way psychiatric disorders are defined. People have studied disorders with a box around them, says Elise Robinson, assistant professor of epidemiology, who has analyzed genetic differences within and between disorders such as schizophrenia, bipolar disorder, depression, and autism, which are usually defined by clinical categories outlined in the Diagnostic and Statistical Manual of Mental Disorders. But Robinson says the idea of distinct boundaries separating these disorders is not necessarily consistent with biology. Genetically, psychiatric disorders look more like Venn diagrams with large overlaps. People with schizophrenia share 60 percent to 70 percent of genome-wide variation with those who suffer bipolar disorder, and about 25 percent with autism.

Similarly, there is no simple dividing line between people who have a psychiatric illness and those who dont. Genetic risk for schizophrenia is not something you either have or dont have, she says. Theres a little bit of risk in all of us. Natural variations in many different genes, she explains, have been shown to relate to the way people perform on tests of cognitive or emotional skills. Schizophrenia may emerge from some combination of factors that are part of normal variation in the development and functioning of the human brain. This is true for other complex diseases and many normal traits, she adds: height, for instance, is largely determined by genetics, but theres no single geneor even handful of genesthat controls it. Its a quality that emerges from many genetic inputs.

Robinson believes that scientists could learn more about these disorders by cutting across diagnostic boxes and studying genetic variants that are linked to multiple traits and disorders. Only by understanding how these variants affect the brain can researchers begin to understand how they contribute both to normal brain function and to the risk of disease.

Such research could help demystify the experiences of people like Andrew LeClerc. He has learned to talk about his schizophrenia as something he struggles with, not something that defines him. He describes his condition as a mental difference.

LeClerc also appreciates that not all the voices in his head are negative: he sometimes hears words of encouragement or helpful warnings. As he speaks, his thoughts dont always follow the linear paths of normal conversation, but they can take him into deeper places; he has a keen understanding of how humans brains create their own realities. He sees an analogy to his condition in the once-expensive glass pieces he has begun collecting from his local dump. Glass that seems like trash, he says, can be reused or recycled, so it isnt really broken. He describes himself the same way: Im fragile, not broken.

It may take decades before genetic research on schizophrenia yields new treatments for people like LeClerc, but clues about the biological underpinnings of schizophrenia could help in other ways. Patients with psychiatric disorders get blamed for those disorders in our culture in a way that people with diseases in other organs dont, says McCarroll. If this research can provide a firmer biological understanding of whats happening in the brain, he says, I would hope that we could generate more empathy.

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Probing Psychoses - Harvard Magazine

3D Artificial Skin Used To Treat Spina Bifida In Rats – Asian Scientist Magazine

Scientists have used artificial skin grafts grown from induced pluripotent stem cells to cover the developing spines of rat fetuses while still in the womb.

Asian Scientist Newsroom | June 14, 2017 | In the Lab

AsianScientist (Jun. 14, 2017) - Researchers from Japan have developed a stem cell-based therapy to treat a severe congenital bone defect known as myelomeningocele. Their findings have been published in Stem Cell Reports.

Myelomeningocele is the most serious and common form of spina bifida, a condition in which the backbone and spinal canal do not close before birth, leaving parts of the spinal cord and nerves exposed.

A baby born with this disorder typically has an open area or a fluid-filled sac on the mid to lower back. Most children with this condition are at risk of brain damage because too much fluid builds up in their brains. They also often experience symptoms such as loss of bladder or bowel control, loss of feeling in the legs or feet, and paralysis of the legs.

To develop a minimally invasive treatment to cover large myelomeningocele defects earlier during pregnancy, the researchers first generated artificial skin from human induced pluripotent stem cells (iPSCs), and then successfully transplanted the skin grafts into rat fetuses with the condition.

We provide preclinical proof of concept for a fetal therapy that could improve outcomes and prevent lifelong complications associated with myelomeningoceleone of the most severe birth defects, said senior study author Professor Akihiro Umezawa of Japan's National Research Institute for Child Health and Development.

Since our fetal cell treatment is minimally invasive, it has the potential to become a much-needed novel treatment for myelomeningocele.

The human iPSCs were generated from fetal cells taken from amniotic fluid from two pregnancies with severe fetal disease (Down syndrome and twin-twin transfusion syndrome). The researchers then used a chemical cocktail in a novel protocol to turn the iPSCs into skin cells and treated these cells with additional compounds such as epidermal growth factor to promote their growth into multi-layered skin.

In total, it took approximately 14 weeks from amniotic fluid preparation to 3D skin generation, which would allow for transplantation to be performed in humans during the therapeutic window of 28-29 weeks of gestation.

Next, the researchers transplanted the 3D skin grafts into 20 rat fetuses through a small incision in the uterine wall. The artificial skin partially covered the myelomeningocele defects in eight of the newborn rats and completely covered the defects in four of the newborn rats, protecting the spinal cord from direct exposure to harmful chemicals in the external environment.

Moreover, the engrafted 3D skin regenerated with the growth of the fetus and accelerated skin coverage throughout the pregnancy period. Notably, the transplanted skin cells did not lead to tumor formation, but the treatment significantly decreased birth weight and body length.

We are encouraged by our results and believe that our fetal stem cell therapy has great potential to become a novel treatment for myelomeningocele, Umezawa said. However, additional studies in larger animals are needed to demonstrate that our fetal stem cell therapy safely promotes long-term skin regeneration and neurological improvement.

The article can be found at: Kajiwara et al. (2017) Fetal Therapy Model of Myelomeningocele with Three-dimensional Skin Using Amniotic Fluid Cell-derived Induced Pluripotent Stem Cells.

Source: Cell Press; Photo: Kazuhiro Kajiwara. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

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3D Artificial Skin Used To Treat Spina Bifida In Rats - Asian Scientist Magazine

Transplants using iPS cells put Riken specialist at forefront of regenerative medicine research – The Japan Times

When she entered medicine in the mid-1980s, Masayo Takahashi chose ophthalmology as her specialty, she said, because she wanted to have a family and thought the discipline would spare her from sudden work calls in the middle of the night, helping her best balance work and life.

Three decades later, the 55-year-old mother of two grown-up daughters is at the forefront of the nations even the worlds research into regenerative medicine.

In September 2014, she offered a ray of hope to scores of patients suffering from a severe eye condition when her team at the Riken institutes Center for Developmental Biology in Kobe succeeded in a world-first transplanting of cells made from induced pluripotent stem (iPS) cells into a human body.

The operation, conducted as a clinical study, involved creating a retinal sheet from iPS cells, which were developed by Shinya Yamanaka, a researcher at Kyoto University. His 2006 discovery of iPS cells, which can grow into any kind of tissue in the body, won him a Nobel Prize in 2012.

During the 2014 procedure, the retinal sheet was transplanted into a female patient in her 70s with age-related macular degeneration (AMD), an eye disorder that blurs the central field of vision and can lead to blindness. The research team used iPS cells made from the patients own skin cells.

Takahashi made history again in March when she and her team carried out the worlds first transplant of retina cells created from donor iPS cells stocked at Kyoto University. The time and cost necessary for the procedure has been significantly reduced by using the cells, which are made from super-donors, people with special white blood cell types that arent rejected by the immune systems of receiving patients.

Takahashi was in Tokyo last week to speak at the Foreign Press Center and later with The Japan Times. She recounted the highlights of her 25-year research and the numerous legal and other challenges she has overcome.

Takahashi points to the day she led that first iPS transplant surgery Sept. 12, 2014 as the high point of her career so far. Because she worked so hard leading up to the surgery to confirm the safety of the retinal cells, she said that when the operation was over, she was relieved and slept very well.

It wasnt the same for Yamanaka, who provided the stem cells to Takahashi, she said, chuckling. Yamanaka-sensei couldnt sleep well after the surgery because he didnt know about the safety of the cells very well. I should have convinced him.

Some researchers have expressed concern that iPS cell-derived cells have a higher risk of developing cancer. But Takahashi said she knew from the outset that the type her team was making, retinal pigment epithelium (RPE) cells, are extremely unlikely to cause tumors. RPE cells make up the pigmented layer of tissue that supports the light-sensitive cells of the retina.

People in the world think iPS cells are very dangerous because we modify the genes, she said. The retinal pigment epithelium cell is very safe. We knew it from the beginning because we have never seen a metastatic tumor from this cell. Ophthalmologists know very well that this cell is very safe and very good.

The Osaka native said she learned of and became fascinated by the possibility of using stem cells for eye diseases in the mid-1990s, when she took a year off from clinical practice at Kyoto University to work as a researcher at the Salk Institute in San Diego. She moved to Riken in 2006.

More than 2 years have passed since that first iPS surgery, but the transplanted cells remain intact. According to Takahashi, it was not the goal of the research from the outset to improve the eyesight of the patient, who suffered from a very severe case of AMD. Before the surgery, the patient required injections of drugs into her eyeball every two months, but her visual acuity was declining. After the surgery, her acuity stabilized, and more importantly, she is happy, feeling that her vision has brightened and widened, Takahashi said.

Many challenges remain, however, to advance the technology and make it commercially available. One of the issues is cost, Takahashi said, adding that it will take until around 2019 before the cost of the iPS treatment for AMD will fall below 10 million. The first surgery in 2014 cost about 100 million in total, much of which was spent to maintain the clean room and culture the cells.

Still, Takahashi sees a huge potential for iPS cell therapy in her field and beyond.

Every disease has potential to be treated by iPS cell-derived cells or ES (embryonic stem) cell-derived cells in the future, she said, responding to a question on the chances of iPS cells being used to treat ALS, a rare, degenerative neurological disease for which there is currently no cure.

She said she has learned through her experience that some patients are very happy with small improvements.

For ALS, at first, I thought, its a systemic, whole-body disease, so I didnt know how they can fix it, she said. But a doctor (who specializes in ALS) said, its OK, if one finger moves, its (still) OK. So I realized that some benefit will come from cell therapy.

A Matter of Health is a weekly series on the latest health research, technology or policy issues in Japan. It appears on Thursdays.

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Transplants using iPS cells put Riken specialist at forefront of regenerative medicine research - The Japan Times

What Are Stem Cells – Checkbiotech.org (press release)

Tissue-specific stem cells

Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut. Stem cells have two key properties: 1) the ability to self-renew, dividing in a way that makes copies of themselves, and 2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.

Tissue-specific stem cells Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found within the adult brain are capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting. Neuron Dr. Gerry Shaw, EnCor Biotechnology Inc. Astrocyte Abcam Inc. Oligodendrocyte Dhaunchak and Nave (2007). Proc Natl Acad Sci USA 104:17813-8 http://www.isscr.org Embryonic stem cells Embryonic stem cells have been derived from a variety of species, including humans, and are described as pluripotent, meaning that they can generate all the different types of cells in the body. Embryonic stem cells can be obtained from the blastocyst, a very early stage of development that consists of a mostly hollow ball of approximately 150-200 cells and is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an inner cell mass from which embryonic stem cells can be obtained. Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed. The fertilized egg and the cells that immediately arise in the first few divisions are totipotent. This means that, under the right conditions, they can generate a viable embryo (including support tissues such as the placenta). Within a matter of days, however, these cells transition to become pluripotent. None of the currently studied embryonic stem cell lines are alone capable of generating a viable embryo (i.e., they are pluripotent, not totipotent). Why are embryonic stem cells so valuable? Unlike tissue-specific (adult) stem cells, embryonic stem cells have the potential to generate every cell type found in the body. Just as importantly, these cells can, under the right conditions, be grown and expanded indefinitely in this unspecialized or undifferentiated state. These cells help researchers learn about early human developmental processes that are otherwise inaccessible, study diseases and establish strategies that could ultimately lead to therapies designed to replace or restore damaged tissues. Induced pluripotent stem cells One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPS cells). These are adult cells (e.g., skin cells) that are engineered, or reprogrammed, to become pluripotent, i.e., behave like an embryonic stem cell. While these iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, it is important to understand that they are not identical. The original iPS cells were produced by using viruses to insert extra copies of three to four genes known to be important in embryonic stem cells into the specialized cell. It is not yet completely understood how these three to four reprogramming genes are able to induce pluripotency; this question is the focus of ongoing research. In addition, recent studies have focused on alternative ways of reprogramming cells using methods that are safer for use in clinical settings. Disease- or patient-specific pluripotent stem cells One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patientspecific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur following transplants from unrelated donors. Moving stem cells into the clinic Clinical translation is the process used to turn scientific knowledge into real world medical treatments. Researchers take what they have learned about how a tissue usually works and what goes wrong in a particular disease or injury and use this information to develop new ways to diagnose, stop or fix what goes wrong. Before being marketed or adopted as standard of care, most treatments are tested through clinical trials. Sometimes, in attempting new surgical techniques or where the disease or condition is rare and does not have a large enough group of people to form a clinical trial, certain treatments might be tried on one or two people, a form of testing sometimes referred to as innovative medicine. For more information on how science becomes medicine, please visit http://www.closerlookatstemcells.org. Current therapies Blood stem cells are currently the most frequently used stem cells for therapy. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation. Additionally, some bone, skin and corneal diseases or injuries can be treated by grafting tissues that are derived from or maintained by stem cells. These therapies have also been shown to be safe and effective. Potential therapies Other stem cell treatments, while promising, are still at very early experimental stages. For example, the mesenchymal stem cell, found throughout the body including in the bone marrow, can be directed to become bone, cartilage, fat and possibly even muscle. In certain experimental models, these cells also have some ability to modify immune functions. These abilities have created considerable interest in developing ways of using mesenchymal stem cells to treat a range of musculoskeletal abnormalities, cardiac disease and some immune abnormalities such as graft-versus-host disease following bone marrow transplant. Remaining challenges Despite the successes we have seen so far, there are several major challenges that must be addressed before stem cells can be used as cell therapies to treat a wider range of diseases. First, we need to identify an abundant source of stem cells. Identifying, isolating and growing the right kind of stem cell, particularly in the case of rare adult stem cells, are painstaking and difficult processes. Pluripotent stem cells, such as embryonic stem cells, can be grown indefinitely in the lab and have the advantage of having the potential to become any cell in the body, but these processes are again very complex and must be tightly controlled. iPS cells, while promising, are also limited by these concerns. In both cases, considerable work remains to be done to ensure that these cells can be isolated and used safely and routinely. Second, as with organ transplants, it is very important to have a close match between the donor tissue and the recipient; the more closely the tissue matches the recipient, the lower the risk of rejection. Being able to avoid the lifelong use of immunosuppressants would also be preferable. The discovery of iPS cells has opened the door to developing patient-specific pluripotent stem cell lines that can later be developed into a needed cell type without the problems of rejection and immunosuppression that occur from transplants from unrelated donors. Third, a system for delivering the cells to the right part of the body must be developed. Once in the right location, the new cells must then be encouraged to integrate and function together with the bodys other cells. http://www.isscr.org Glossary Blastocyst A very early embryo that has the shape of a ball and consists of approximately 150-200 cells. It contains the inner cell mass, from which embryonic stem cells are derived, and an outer layer of cells called the trophoblast that forms the placenta. Cell line Cells that can be maintained and grown in a dish outside of the body. Clinical translation The process of using scientific knowledge to design, develop and apply new ways to diagnose, stop or fix what goes wrong in a particular disease or injury. Differentiation The process of development with an increase in the level of organization or complexity of a cell or tissue, accompanied by a more specialized function. Embryo The early developing organism; this term denotes the period of development between the fertilized egg and the fetal stage. Embryonic stem cell Cells derived from very early in development, usually the inner cell mass of a developing blastocyst. These cells are self-renewing (can replicate themselves) and pluripotent (can form all cell types found in the body). Induced pluripotent stem (iPS) cell Induced pluripotent cells (iPS cells) are stem cells that were engineered (induced) from non-pluripotent cells to become pluripotent. In other words, a cell with a specialized function (for example, a skin cell) that has been reprogrammed to an unspecialized state similar to that of an embryonic stem cell. Innovative medicine Treatments that are performed on a small number of people and are designed to test a novel technique or treat a rare disease. These are done outside of a typical clinical trial framework. In vitro fertilization A procedure in which an egg cell and sperm cells are brought together in a dish to fertilize the egg. The fertilized egg will start dividing and, after several divisions, forms the embryo that can be implanted into the womb of a woman and give rise to pregnancy. Mesenchymal stem cells Mesenchymal stem cells were originally discovered in the bone marrow, but have since been found throughout the body and can give rise to a large number of connective tissue types such as bone, cartilage and fat. Multipotent stem cells Stem cells that can give rise to several different types of specialized cells, but in contrast to a pluripotent stem cell, are restricted to a certain organ or tissue types. For example, blood stem cells are multipotent cells that can produce all the different cell types that make up the blood but not the cells of other organs such as the liver or brain. Pluripotent stem cells Stem cells that can become all the cell types that are found in an implanted embryo, fetus or developed organism. Embryonic stem cells are pluripotent stem cells. Self-renewal The process by which a cell divides to generate another cell that has the same potential. Stem cells Cells that have both the capacity to self-renew (make more stem cells by cell division) and to differentiate into mature, specialized cells. Tissue-specific stem cells (also known as adult or somatic stem cells) Stem cells found in different tissues of the body that can give rise to some or all of the mature cell types found within the particular tissue or organ from which they came, i.e., blood stem cells can give rise to all the cells that make up the blood, but not the cells of organs such as the liver or brain. Totipotent stem cells Stem cells that, under the right conditions, are wholly capable of generating a viable embryo (including the placenta) and, for humans, exist until about four days after fertilization, prior to the blastocyst stage from which embryonic stem cells are derived.

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What Are Stem Cells - Checkbiotech.org (press release)

Trends in Drug Discovery Outsourcing: A Perspective – BSA bureau (press release)

Seven drugs of the current top-10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products.

Dr Subir Basak Chief Business Officer, GVK Biosciences

Over the last two decades, the Pharmaceutical industry has seen a radical change. The unprecedented downsizing of the internal discovery of big pharmaceuticals, patent expiration, shift towards biologics have seen a surge in the externalization and outsourcing activities. As the industry is looking for new sources of discovery and innovation with limited resources, there is a growing preference to move towards externalization and willingness to embrace the concept of outsourcing.

Seven drugs of the current top- 10 best selling drugs are biologics, the penetration of biologic drugs is expected to reach 30% by 2020 of the global pharmaceutical market and some of the key modalities include monoclonal antibodies, recombinant proteins, peptides, cell and gene therapy products. Global R&D spend in the biopharmaceutical industry is estimated to be $194 billion in 2016 and according to industry experts, 75-80% of the expenses can be outsourced. However, current penetration rate is around 58% which presents a huge opportunity for the CROs to tap the Trends in Drug Discovery Outsourcing: A Perspective market. The global pharmaceutical outsourcing market was estimated to be $113.7 billion in 2016 and out of which 49% is accounted for CROs. Among the $55.7 billion CRO market, 31.2% accounts for discovery-based service i.e. $17.4 billion in 2016 and the remaining 68.8% accounts for Preclinical and clinical services.

Biology related services segment is a high growth area with huge potential and expected to grow faster at a CAGR of 17.2% compared to the small molecules segment due to increase in budget allocations for R&D by biopharmaceutical companies.

The drug discovery CRO industry is witnessing increased consolidation. Many Asia-based companies are increasing their foothold in Europe and North America. GVK BIO, a Contract Research & Development Organization (CRDO) from India has taken over Aragen Bioscience. Aragen has early stage discovery biologics capabilities and played a leading role in oncology and fibrosis based animal models for preclinical biotechs in bay area. Similarly, ChemPartner established research facility in South San Francisco. Also, WuXi AppTec acquired HD Biosciences (HDB), a biology focused preclinical drug discovery CRO.

Advancement in drug discovery technologies such as iPS cells, automated high content screening, patch clamp, gene editing and DNAencoded libraries have expedited the drug discovery process with increased efficiency. There is an increased interest in the use of DNAencoded libraries (small molecules tagged with DNAs) by major pharma companies.Majority of the companies offering DNA-encoded library services are from US (DiCE, X-Chem, Ensemble therapeutics) and Europe (Nuevolution, Vipergen, Cominnex, Philochem). Thereseems to be very little competition in APAC. This trend should push some of the CROs from APAC region to acquire companies with proprietary technology in DNA-encoded libraries or to build capabilities and this seems likely to be a focus point for majority of the CROs especially from APAC.

Evolving business models including risk-based and insourcing are facilitating better collaboration between pharmaceutical companies and CROs. Some of the companies established a new business model known as insourcing which is a new sourcing for pharma where CROs work on-site at customer location in an integrated fashion. This new model provides outstanding performance with efficient cost and time.

CROs should build capabilities to differentiate in the area of Target Identification/Target Validation on how to use human disease pathology knowledge/primary tissues from humans clubbed with Omics knowledge to further validate the concepts. As most of the CROs propose targets from literature and sponsor companies consider it as risky option to invest in such projects without substantial evidences. As a de-risking strategy some CROs are investing internally and validating the concept by siRNA, knockdown approaches and take the concept to a level-up and then approach the sponsors companies who are working in similar area. This approach would increase the sponsor confidence in the CRO program.

There is a huge demand for the novel therapeutics addressing the unmet needs, for example, there are no FDA approved drugs or any therapies for NASH treatment and there is a tremendous opportunity for CROs to work on novel targets, preclinical models and biomarker to come-up with some early stage assets for partnering. Owing to market attractiveness, there is funding provided by venture capitalists to promising players, while some investors are even launching new companies to specifically work on NASH projects. For instance in February 2017, Versant Ventures formed Jecure Therapeutics through $20 million investment for NASH program development. Similarly, Third Rock Ventures formed Pliant Therapeutics with $45 million investment for TGF- signaling based NASH treatment. These companies could potentially outsource majority of the work to CROs in APAC region.

Asia is emerging as a preferred destination for outsourcing drug discovery activities due to the vast availability of skilled manpower, lower costs, favorable regulatory environment and quality data. In addition the local governments are focusing on development of healthcare and pharmaceutical industryby ensuring focus on high quality & compliance in terms of higher regulatory surveillance and training programs. Japan being the second largest pharmaceutical market in the world provides huge opportunity for CROs from APAC. Chinese and Indian pharmaceutical markets are one of the fastest growing in the world and are considered to be the preferred locations for drug discovery outsourcing primarily because of the end-to-end technological capabilities developed over several years. Asian CROs have strong capabilities in biologics research services and built new technology platforms for high-throughput screening, genomics and proteomics research panel screening, enzymatic, and binding assays. They are also well equipped with transgenic and disease animal models that have been developed for target validation, efficacy, and safety studies, thereby providing clients with end-to-end services. Indian CROs typically focus more on new chemical entities and offer integrated discovery services at much lower cost.

Therapeutic area gap analysis research indicates that the key contract research organizations in Asia pacific region are majorly focusing on Oncology, metabolic diseases, Inflammation and CNS. However, majority of Pharma companies in addition to the above therapeutic areas are also focusing on other areas like cardiovascular, immunology, infectious diseases. Since there is a high gap in these therapeutic areas, the CROs should increase their focus in order to tap the opportunity.

Growth in biologics research and orphan drugs, innovative technological platforms and evolving business models encourage pharma and biotech companies to outsource. Even though, big pharma is moving towards research institutions and academia to accelerate knowledge and leverage innovation and technology platforms, they lack the infrastructure to move the drugs from early stages of drug discovery. These factors are expected to enhance drug discovery outsourcing market in APAC region for the coming years.

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Trends in Drug Discovery Outsourcing: A Perspective - BSA bureau (press release)

IPS Cell Therapy – Page 5423 IPS Cell Therapy

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Stem Cell Research is an amazing field right now, and promises to be a powerful and potent tool to help us live longer and healthier lives. Just last month, for example, Stem Cell Therapy was used to restore sight in patients with severe retinal deterioration, allowing them to see clearer than they had in years, or even decades.

Now, there is another form of Stem Cell Treatment on the horizonthis one of a very different form. Stem Cells have now been used as a mechanism to deliver medical treatment designed to eliminate cancer cells, even in hard to reach places. One issue with current cancer treatments is that, treatments that are effective at treating tumors on the surface of the brain cannot be performed safely when the tumor is deeper within the brains tissues.

Stem Cells have the fantastic ability to transform into any other kind of cell within the human body, given the appropriate stimulation. As of today, most of these cells come from Embryonic Lines, but researchers are learning how to backwards engineer cells in the human body, reverting them back to their embryonic state. These cells are known as Induced Pluripotent Stem Cells.

How Does This Stem Cell Cancer Treatment Work?

Using genetic engineering, it is possible to create stem cells that are designed to release a chemical known as Pseudomonas Exotoxin, which has the ability to destroy certain tumor cells in the human brain.

What is Pseudomonas Exotoxin?

Pseudomonas Exotoxin is a compound that is naturally released by a form of bacteria known as Pseudomonas Aeruginosa. This chemical is toxic to brain tumor cells because it prevents polypeptides from growing longer, essentially preventing the polypeptides from growing and reproducing. When used in a specific manner, this toxin has the ability to destroy cancerous and malignant tissue without negatively impacting healthy tissue. In addition to its potential as a cancer treatment, there is also evidence that the therapy could be used for the treatment of Hepatitis B.

PE and Similar Toxins Have been Used Therapeutically in the Past

As of now, this chemical, which we will refer to for the rest of the article as PE, has been used as a cancer treatment before, but there are major limitations regarding the use of PE for particular cancers, not because of the risks of the treatment, but because of the lack of an effective method to deliver the medication to where it is needed.

For example, similar chemicals have been highly effective in the treatment of a large number of blood cancers, but havent been nearly as effective in larger, more inaccessible tumors. The chemicals break down or become metabolized before they can fully do their job.

How do Stem Cells Increase the Effectiveness of PE Cancer Treatment

Right now, PE has to be created in a laboratory before it is administered, which is not very effective for these embedded cancers. By using Stem Cells as an intermediary, it is possible to deliver the medication to deeper areas of the brain more effectively, theoretically highly increasing the efficacy of the treatment.

The leader of this Stem Cell Research is Harvard researcher Dr. Khalis Shah. His goal was to find an effective means to treat these deep brain tumors which are not easily treated by methods available today. In utilizing Stem Cells, Dr. Shah has potentially found a means by which the stem cells can constantly deliver this Cancer Toxin to the tumor area. The cells remain active and are fed by the body, which allows them to provide a steady stream of treatment that is impossible to provide via any other known method.

This research is still in its early stages, and has not yet reached human trials, but in mice, the PE Toxin worked exactly as hypothesized and was able to starve out tumors by preventing them from replicating effectively.

Perhaps this might seem a bit less complicated than it actually is. One of the major hurdles that had to be overcome was that this Toxin would normally be strong enough to kill the cell that hosted it. In order for the Stem Cells to release the cancer, they had to be able to withstand the effects of PE, themselves. Using genetic engineering, Dr. Shah and his associates were able to create a cell that is capable of both producing and withstanding the effects of the toxin.

Stem Cell delivered medical therapy is a 21st century form of medical treatment that researchers are just beginning to learn how to effectively utilize. Essentially, this treatment takes a stem cell and converts it into a unique symbiotic tool capable of feeding off of the host for energy in order to perform a potentially life-saving function. Its really quite fascinating.

How Does PE Not Damage or Kill Brain Cells Indiscriminately?

You might be concerned about the idea of a patient having a toxin injected into the brain to cure a disease. It sounds almost like a dangerous, tribal, homeopathic remedy. In reality, the researchers have been able to harness the destructive power of the toxin and re-engineer it so that it directly targets cancer cells while having limited negative effects on healthy, non-cancerous tissue.

The toxin does its damage after it has been absorbed by a cell. By retooling the toxin so that it does not readily absorb into healthy cells, the dangers associated with having such a potentially dangerous toxin in the brain are seriously and significantly mitigated.

Beyond that, Dr. Shah and his associates have been able to take steps to effectively turn off PE while it is inside the host stem cell, and only activates when it has entered the cancerous tissue. Dr. Shah explains that, although this research has only been conducted in animal subjects, there is no known reason why the effectiveness and safety of the treatment would not be applicable to human patients.

In this treatment, surgeons remove as much of the tumor as possible from the brain, and insert the engineered Stem Cells submerged in a sterile gel in the area where the tumor was removed or partially still exists. Researchers found that, when they used this treatment on laboratory rats, they could tell through imaging and analysis that the modified PE toxin effectively killed the cancer cells, and that this cancer treatment effectively lengthened the life of the rat, as compared to control subjects.

Whats the Next Step?

Of course, cancer treatment is far more complex than a single treatment, no matter how effective that treatment may be. Because human cancer treatment is a comprehensive therapy approach, the end goal of this research is to create a form of therapy in which the method used in animal subjects is combined with other existing approaches, increasing and maximizing the effectiveness of the comprehensive treatment.

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A recent change in how well we understand stem cells may make it easier for scientists and researchers to gather stem cells for use in scientific research as well as medical application. A new study was released in the research publication, Cell, which was performed by representatives from the University of California San Francisco.

One of the issues which hinder the use of stem cells as a more widespread treatment or field of research is that researchers and patients have a bottleneck of available healthy stem cell lines which can be used for research. Researchers hope that this new discovery will allow future scientific discoveries and applications in the areas of creating new and healthy tissue for patients with kidney failure or any other form of organ tissue failure. The future of medical therapy lies with Stem Cell Research, but many other forms of treatment, including Hormone Replacement Therapy, are already in practice today.

Researchers have discovered that it is possible to essentially flip a switch in an adult cell, reverting it back to the preliminary state at which cells existed in one of the earliest stages of developmentthe embryonic stem cell. Medical researchers hypothesize that Stem Cell treatments could be used for a variety of medical health issues which plague the world today, including kidney failure, liver disease, and Type-1 and Type-2 Diabetes.

Use of Embryonic Stem Cells Contentious

There is an ethical issue in Stem Cell Research today. Many Pro-Life Advocates are vociferously against the use of Embryonic Stem Cells harvested from procedures such as fertility treatments designed for conception. They believe that the use of embryonic stem cells harvested from donors and couples looking to conceive is unethical.

Using current research, it may be possible to bypass this ethical quandary completely by using adult cells and converting them into embryonic stem cells. Furthermore, because these stem cells are genetic derivatives of the patient from which the adult cells were harvested, this potentially paves the way for patient-specific medical treatments using stem cells.

After adult cells have been converted back into Embryonic Stem Cells, it will be possible to convert them into any possible cell that the patient needs or would benefit from.

Hijacking the Blueprint of the Cell Allows Scientists to Revert Adult Cells to their Earliest State

Researchers have increased the capacity to produce Embryonic Stem Cells by identifying previously unrecognized biochemical processes which tell human cells how to develop. In essence, researchers have discovered how the body blueprints cells, and can change the blueprints so that a new cell is made.

By utilizing these newly recognized pathways, it is possible to create new stem cells more quickly than ever before. One of the researchers explains the implications of this research. Dr. Miguel Ramalho-Santos is an associate professor of obstetrics, medicine, and cancer research at the University of California San Francisco. Dr. Ramalho-Santos is also a member of the Broad Center of Regenerative Medicine and Stem Cell Research.

He explains that these stem cell discoveries have the ability to alter the way that the medical sciences can take advantage of stem cells with regard to both cancer research and regenerative medicine. Dr. Ramalho-Santos was the lead researcher for this study, and the research was largely funded by the Director of the National Institutes of Health New Innovator Award, granted to promising young researchers which are leading highly innovative and promising medical research studies.

Dr. Ramalho-Santos research builds off of earlier research which discovered that it was possible to take adult cells and turn them back into embryonic stem cells. These stem cells dont have any inherent aging processes, and they can be turned into any other kind of tissue. In the process of this conversion, the adult cells lose all of their unique characteristics, leaving them in an ultimately immature and malleable state.

This earlier research was conducted by researchers from UC San Francisco in partnership with Dr. Shinya Yamanaka from Kyoto University and Gladstone Institutes. These entities all gained a piece of the Nobel Prize in Physiology or Medicine from their part in the study.

Pluripotent Stem Cells vs. Embryonic Stem Cells

Thus far, weve described these cells as Embryonic Stem Cells, but in fact, the more accurate term for these cells are Induced Pluripotent Stem Cells (IPS). These cells are biologically and functionally similar to Embryonic Stem Cells, but have a different name because they are sourced from adult cells. The difference between Induced Pluripotent Stem Cells and Embryonic Stem Cells is that Induced Pluripotent Stem Cells do seem to retain some of the characteristics of their previous state, which appears to limit their ability to convert into any other type of cell. This new research identifies new pathways by which it may be possible to increase the number of cells that an individual IPS Cell can turn into, perhaps allowing them to convert into any other kind of human cell.

Induced Pluripotent Stem Cells are not explicitly considered an alternative to Embryonic Stem Cells, but are considered a different approach to produce similar cells. If researchers fully uncover the mechanisms of how to reprogram these cells, it will lower many barriers to stem cell research and the availability of stem cell treatments.

As of today, researchers have figured out how to make these Induced Pluripotent Stem Cells, but the percentage of adult cells which are reverted successfully is quite low, and frequently, these cells still show some aspects of specialization, which limits their use.

How Do Scientists Make Stem Cells From Adult Cells?

There are genes within every cell which have the ability to induce pluripotency, reverting the cell to an earlier stage of specialization. The initial stage of this process is the result of activating Yamanaka Factors, specific genes that initiate this reversion process.

As of today, this process of de-maturation is not completely understood, and researchers realized from the start that the cells they created were not truly identical to Embryonic Stem Cells, because they still showed signs of their former lives, which often prevented them from being successfully reprogrammed.

The new research conducted by Dr. Ramalho-Santos appears to increase our knowledge regarding how these cells work, and how to program them more effectively. Dr. Ramalho-Santos and his team discovered more genes associated with these programming/reprogramming processes, and by manipulating them, they have increased the viability and range of particular stem cells.

It appears that these genetic impulses are constantly at play to maintain the structure and function of a cell, and that by systematically removing these safeguards, it is possible to increase the ability to alter these cells.

This research increases researchers ability to produce these stem cells, by increasing the ability of medical scientists to produce adequate numbers of stem cells, while also increasing the range of potential treatment options by more effectively inducing the total pluripotency which is available in Embryonic Stem Cells. This research may also help scientists treat certain forms of cancer which are the result of malfunctions of these genes.

Dr. Patrick W. Thomas Published 7:00 p.m. ET May 30, 2017 | Updated 9 hours ago

Dr. Patrick W. Thomas, chief of cardiology at New York-Presbyterian Hudson Valley Hospital, supports state legislation to raise the age for tobacco sales to 21. Dr. Thomas is also president of the Board of Directors for the Putnam County Division of the American Heart Association. Video by Nancy Cutler/lohud Wochit

Those who seek support to stop smoking are more likely to succeed.(Photo: AndreyPopov, Getty Images/iStockphoto)

I see it in my cardiology practice each day the deadly effects of smoking: The obvious health implications, the attempts to quitand the resignation that comes when those quitting attempts fail. Tobacco addiction causes heart disease, damage to arteries throughout the body, chronic and debilitating breathing issues, stroke, aneurysms, cancer. The list goes on.

I prescribe medications (such as nicotine replacement therapies) and offer information for group or individual counseling. Most patients who smoke want to quit but the addiction is just too strong.

As a health-care provider, it is my job to speak out to break the cycle of tobacco addiction, and thats exactly what legislation thats been proposed to raise the age of sale for tobacco products in New York would do and our lawmakers have just a few weeks to move on it.

WESTCHESTER: County mulls age change for tobacco sales

TOMPKINS COUNTY: Legislators raise tobacco age to 21

Sponsored in the Senate by Sen. Diane Savino (S03978) and in the Assembly by Assemblywoman Linda Rosenthal (A0273), the legislation will raise the legal sale age for tobacco products from 18 to 21 statewide.

I know that not one of my patients who smokes would say he or she is glad to have started smoking. Some admit they wont live their lives without it, and some have paid a high price for their addiction but its too hard for them to quit.

And any of those smokers, most of whom started when they were young, would say they dont want to see future generations become addicted to deadly tobacco. Not their kids, grandkids or neighbors. We know that 95 percent of smokers started before age 21. Young people are warned of the reality of tobaccos addiction, but thats not enough we need to do all that is possible to keep these deadly products away from our children.

New York state lawmakers are considering an increase in the age to legally buy tobacco products from age 18 to 21. Joseph Spector, Albany Bureau

The Tobacco 21 bill, as it is known, will not totally prevent smoking. It will not help those who already have started smoking their addiction is likely already too strong. But it can help prevent others from starting. It is another tool for helping keep tobacco out of the hands of high school kids.

Kids tell us that its easy to get tobacco from older kids. Preventing the flow of products from older kids to younger kids is critical. Not many 21-year-olds are still in high school social circles, but plenty of 18- and 19-year-olds are and they supply the cigarettes, chew, and other products to those younger than them.

And the tobacco industry knows it. Theyve been on the record for years saying that laws such as this would gut their next generation of smokers.

As doctors, parents, lawmakers, isnt that exactly what we should be doing? Doing everything we can to prevent unnecessary deaths and illness caused by tobacco?

I commend the work thats been done across all corners of our state to drive this sort of regulation on the local level. From Tompkins County to New York City, and in nearby Orange and Sullivan counties, local leaders have taken this issue head on and have seen widespread support. In fact, to date, more than 55 percent of New Yorkers already livein an area covered by Tobacco 21 legislation. Its a good start, but a mishmash of town and county laws wont get the job done. We need statewide action on this public health crisis.

I urge the New York State Legislature to work to pass Tobacco 21 legislation this session.

The writer is chief of cardiology at New York-Presbyterian Hudson Valley Hospital and president of the Board of Directors for the Putnam County Division of the American Heart Association.

Dr. Patrick W. Thomas(Photo: SUBMITTED/Howard Copeland of Scotts Camera in Peekskill)

Read or Share this story: http://www.lohud.com/story/opinion/contributors/2017/05/30/cardiologist-tobacco-sales-21/354055001/

Original post: Take it from a cardiologist: Tobacco sales should be restricted to 21 and over The Journal News | LoHud.com

TAIPEI, Taiwan, May 30, 2017 /PRNewswire/ TaiGen Biotechnology Company, Limited (TaiGen) today announced that it has submitted a New Drug Application (NDA) for the intravenous formulation of Taigexyn (Nemonoxacin) to the China Food and Drug Administration (CFDA). Taigexyn is a novel non-fluorinated quinolone antibiotic.The NDA submission is supported by a pivotal Phase 3 trial comparing intravenous formulations of Taigexyn 500 mg to levofloxacin 500 mg in 518 patients with moderate to severe community-acquired pneumonia. The clinical success rates were 91.8% for Taigexyn vs. 85.7% for levofloxacin and Taigexyn was shown to be non-inferior to levofloxacin meeting the primary endpoint of the pivotal trial.

About Taigexyn Taigexyn is a novel broad spectrum antibiotic with excellent efficacy against drug-resistant bacteria available in both oral and intravenous formulations. The oral formulation is already approved for marketing and launched in Taiwan and mainland China. In addition, Taigexyn is also partnered in Russia, Commonwealth Independent States, Turkey, Mexico, Brazil and the Latin American territory for a total 32 countries worldwide.

Link: TaiGen Biotechnology Announces Submission of New Drug Application for Taigexyn Intravenous Formulation to the PR Newswire (press release)

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, DC 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): May30, 2017 (May 24, 2017)

PUMA BIOTECHNOLOGY, INC.

(Exact Name of Registrant as Specified in its Charter)

10880 Wilshire Boulevard, Suite 2150

Los Angeles, California 90024

(Address of principal executive offices) (Zip Code)

(424) 248-6500

(Registrants telephone number, including area code)

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (240.12b-2 of this chapter).

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

On May24, 2017, Puma Biotechnology, Inc. (the Company) announced that the U.S. Food and Drug Administrations (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 12 to 4 to recommend approval of PB272 (neratinib) for the extended adjuvant treatment of HER2-positive early stage breast cancer based on finding that the risk-benefit profile of neratinib is favorable. Neratinib is an investigational therapy for the extended adjuvant treatment of early stage HER2-positive breast cancer that has previously been treated with a trastuzumab containing regimen.

ODAC is an independent panel of experts that evaluates data concerning the efficacy and safety of marketed and investigational products for use in the treatment of cancer and makes appropriate recommendations to the FDA. Although the FDA will consider the recommendation of the panel, the final decision regarding the approval of the product is made by the FDA solely, and the recommendations by the panel are non-binding.

SIGNATURE

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IPS Cell Therapy - Page 5423 IPS Cell Therapy

Stem-cell therapy for cancer comes closer home – The New Indian Express

BENGALURU:Full-fledged treatment for cancer and bone-related ailments using stem-cell within the state could soon be a possibility if a plan of a world renowned surgeon from the state succeeds.

Dr A A Shetty is a highly decorated orthopedic surgeon and professor based in the UK who won the Nobel equivalent of surgery called the Hunterian Medal, this year. In his aim to bring about next level cancer and orthopedic treatment, he has already set up two big stem cell research labs - one in Dharwad and another in Mangaluru, a few years back at a cost of around 20 to 25 crore. A hospital that will treat stem-related ailments has also been envisaged at a total cost of around Rs 200 to 250 crore.

Setting up the labs is part of a three-step goal. After setting up the labs, the next step will be producing the stem cells, whether it be for bone ailments, treatment for cervical cancer etc. Then the third step will be the application of these stem cells through our hospital or through tie-ups with other hospitals. I have already received the funding for setting up the hospital, says Dr Shetty in an interaction with CE in Bengaluru. He is originally from a small village called Asode in Udupi district.

The lab in Dharwad is located at SDM College and is being backed by Shri Dharmasthala Manjunatheshwara and will be primarily working on blood cancer and thalassemia treatment. The one in Mangaluru is located at K.S. Hegde Medical Academy (KSHEMA) and is backed by the NITTE group. It will work on cartilage and bone fracture treatments.The effort is no doubt for profit. We will charge the rich but the poor will be treated for free at our hospital, he says.

Already, Shetty has recruited a number of top stem cell researchers from the state who are presently abroad. I have recruited researchers who were doing their postdoc studies in Japan, South Korea. Presently there are four of them working at the two labs, he says. Shetty ultimately wants to settle in Karnataka and hopes to achieve his goal by 2020. The third stage of his plan also requires expertise in various cutting edge technologies such as robotics, computing and he will also be recruiting people who specialize in these fields.

Cancer Vaccination

Shetty also hopes to make cancer vaccination a possibility. Giving an example of cervical cancer, Shetty says, Few cancers can be vaccinated. Cervical cancer, one of the most rampant cancers, is one of them. We will use stems derived from iPS cell. In the UK, the vaccine cost 60 pounds. Our aim is to develop it and sell it at a very low cost, as low as Rs 100, he adds. Induced Pluripotent Stem Cells or iPS Cells are derived from the blood and skiwwn cells and can be reprogrammed to provide an unlimited source of any type of human cell.

Stem cells for Arthritis In 2013, Shetty devised a minimally invasive procedure to treat arthritis using stem cells. When the cartilage between the bones begin to erode, the bones rub against each other and cause severe pain. Shetty treated a patient suffering from knee arthritis. He drilled a hole into the patients knee bone and released stem cells that could grow into the cartilage. In all, the procedure lasted just 30 minutes. Shetty has already done as many as two dozen such procedures in India.

Trauma Center Shetty also says that he wants to develop and provide integrated trauma services. If a patient survives the golden hour then he/she can be saved. Majority die in the first hour of trauma. My integrated services will have specialized suits that will help reduce blood loss and will have other know-how. I am negotiating with the International Rotary on this, he adds. This may be established either in Mangalore or Bangalore.

Dr Vishal Rao, head and neck oncology surgeon at HCG Hospitals says that stem cells research is in the mid-stage of development and has great potential to grow in India. The IT and BT ministry is already taking great steps by encouraging startups on these lines, starting various schemes, he says. Vishal also pointed out that a number of private organizations, hospitals and individuals like those like Dr Shetty are also investing in the field.

Original post:
Stem-cell therapy for cancer comes closer home - The New Indian Express

Lab-grown blood stem cells – Nature Middle East

News

Published online 22 May 2017

Two teams of Arab and American researchers are tantalizingly close to generating primordial blood stem cells in the lab.

Louise Sarant

Hematopoietic stem and progenitor cells (HSPC) from human iPS cells. Rio Sugimura Two teams of scientists have developed methods that make lab-grown blood stem cells a realistic prospect a goal for hematology researchers since human embryonic stem (ES) cells were first isolated in 1998.

Scientists have previously succeeded in genetically reprogramming skin cells to make pluripotent stem (iPS) cells, which are later used to generate multiple human cell types. However, the ability to induce blood stem cells that self-regenerate, for the treatment of millions affected by blood cancers and genetic disorders, has eluded researchers.

The two papers newly published in Nature describe methods that pave the way for safe, artificial and bona fide hematopoietic stem cells (HSCs) generation. Hematopoietic stem (HSC) cells are the common ancestor of all cells created in the body, producing billions of blood cells every day.

This bears major implications for cell therapy, drug screening and leukemia research. The root causes of blood diseases can be scrutinized and creating immune-matched blood cells, derived from a patients own cells, is now conceivable.

The first team, based at the Boston Childrens Hospital, has generated blood-forming stem cells (HSCs) in the lab using pluripotent stem cells for the first time.

Were tantalizingly close to generating bona fide human blood stem cells in a dish, says senior investigator George Daley, who heads the research lab in Boston Childrens Hospitals stem cell program and who is dean of Harvard Medical School. This work is the culmination of over 20 years of striving.

Ryohichi Rio Sugimura, the studys first author and a postdoctoral fellow in the Daley Lab, says his team exposed human pluripotent stem cells (both ES and iPS cells) to chemical signals to prompt them to differentiate into specialized cells and tissues during embryonic development.

"Sugimura and his colleagues delivered transcription factors proteins that control and regulate the transcription of specific genes into the cells using a lentivirus, a vector to deliver genes. The resultant cells were transplanted to immune deficient mice, where human blood and immune cells were made, he says.

A few weeks after the transplant, a small number of rodents were found to be carrying multiple types of blood cells in their bone marrow and blood; cells that are also found in human blood. This is a major step forward for our ability to investigate genetic blood disease, says Daley.

The second team, a group of scientists from Weill Cornell Qatar and Weill Cornell Medicine in New York, used mature mouse endothelial cells cells that line blood vessels as their starting material for generating HSCs.

Image of human CD45+ blood cells differentiated from iPS cells. Rio Sugimura Based on previous work, we hypothesized that endothelial cells are the mastermind of organ development, explains Jeremie Arash Rafii Tabrizi, paper co-author and researcher at the stem cell and microenvironment laboratory at Weill Cornell Medicine, Qatar.

The team isolated the cells, and then pushed key transcription factors into their genomes. Between days 8 and 20 into the process, the cells specified and multiplied.

Our research showed that endothelial cells can be converted into competent HSCs with the ability to both regenerate the myeloid and lymphoid lineage, he explains.

The method brings hope for people afflicted with leukemia requiring HSCs transplantation, or genetic disorders affecting the myeloid or lymphoid lineages. The clinical generation of HSCs, derived from the same individual, can eventually help scientists correct genetic abnormalities.

As exciting as the two studies are, rigorous tests are still required to check the normality of lab-grown cells before the clinical phase, says Alexander Medvinsky, professor of hematopoietic stem cell biology at the University of Edinburgh Medical Research Council Centre for Regenerative Medicine. Medvinsky was not involved in either study.

The risks of infusion of genetically engineered cells in humans should not be underestimated, he weighs in. Tests and trials to generate safe fully functional human blood stem cells may take many years, in contrast to similar assessment in short-living mice. It is not clear now whether blood stem cells can become cancerous in the longer term.

He adds however that this type of research is exactly what is required to potentially meet clinical needs.

doi:10.1038/nmiddleeast.2017.89

See more here:
Lab-grown blood stem cells - Nature Middle East

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