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Home – Cell & Gene Therapy World 2018 – Meet the Future of …

“The event reflected the fantastic growing enthusiasm around cell and gene therapy, including small and large companies, investors and regulators. It was great to see everyone so engaged and so positive. The event really gives you the pulse of what is happening right now in cell and gene therapy.”

Vice President, Regulatory Science, Bluebird Bio, Inc

Great program, great people, great venue.

Managing Director, EUFETS GmbH

Dynamic, interesting and highly interactive event that promotes exchange and networking in highly specialized field of gene therapy.

Associate Director, Powell Gene Therapy Center, University of Florida

“Phacilitate provides a unique forum, bringing together research, process development, and commercial leaders on the cutting edge of cell, gene, and immunotherapy. A great conference for anyone wanting a comprehensive view of the field.”

Vice President, Research & Product Development, Dendreon

“It was all business. Ive never been to an event where over 80% of the conversations I had were constructive to my business objectives.”

Acquisition & Business Development Manager, BioMedical Materials, Chemelot Campus B.V.

Great way to expand network with global experts in cell and gene therapy who are facing similar challenges.

Director, Strategy and Engagement, GSK

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Severe hyponatremia due to hypopituitarism with adrenal …

Objective: Adrenal insufficiency due to hypopituitarism can lead to severe hyponatremia with potentially fatal consequences. Prompt diagnosis and adequate hormonal replacement therapy are essential to block an otherwise unfavorable course and to re-establish a healthy life. Unfortunately, this condition is often misdiagnosed. Design: Case report. Setting: Intensive Care Unit of a teaching hospital. Patient: A 76-yr-old man with refractory hypotension, acute myocardial infarction, and left ventricular dysfunction, secondary to severe chronic pan-hypopituitarism, associated with severe hyponatremia. Methods and main results: The patient underwent mechanical ventilation and continuous venous-venous hemodiafiltration, for severe respiratory and renal insufficiency. A hormonal replacement therapy with T4, hydrocortisone, and nandrolone was started and the patient was discharged to a rehabilitation facility after 31 days of hospitalization. Conclusions: Hypopituitarism with secondary adrenal insufficiency is often misdiagnosed at an early stage and a high degree of suspicion is necessary for early diagnosis. Determination of plasma cortisol level in patients with hyponatremia not explained by other causes should always be obtained.

Key-wordsHyponatremiapan-hypopituitarismadrenal insufficiencymyocardial infarctionhypothyroidism

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Yatagai T, Kusaka I, Nakamura T, et al. Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency. Eur J Endocrinol 2003, 148: 2216.


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Italian Society of Endocrinology (SIE)2007

Severe hyponatremia due to hypopituitarism with adrenal …

Recommendation and review posted by Bethany Smith

Stem Cell Basics I. |

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic “somatic” or “adult” stem cells. The functions and characteristics of these cells will be explained in this document. Scientists discovered ways to derive embryonic stem cells from early mouse embryos more than 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be “reprogrammed” genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.


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Stem Cell Basics I. |

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Drug may reduce female cancer patient infertility risk, according to study – Life Science Daily

Researchers recently determined that an existing drug may protect premenopausal women from infertility following cancer treatments.

A study funded by the National Institutes of Health with findings published in Genetics revealed the benefits of checkpoint protein (CHK2) in mice.

Officials said women treated for cancer with radiation or certain chemotherapy drugs are commonly rendered sterile adding women are born with a lifetime reserve of oocytes or immature eggs but those oocytes are among the most sensitive cells in the body and may be wiped out by cancer treatments.

Investigators said CHK2 functions in a pathway that eliminates oocytes with DNA damage, a natural function to protect against giving birth to offspring bearing new mutations. When they irradiated mice lacking the CHK2 gene, the oocytes survived and eventually repaired the DNA damage, with the mice birthing healthy pups.

It turns out there were pre-existing CHK2 inhibitor drugs that were developed, ironically enough, for cancer treatment, but they turned out not to be very useful for treating cancer, said John Schimenti, the papers senior author and Cornell University professor in the Departments of Biomedical Sciences and Molecular Biology and Genetics. The one major concern is that even though these irradiated oocytes led to the birth of healthy mouse pups, its conceivable that they harbor mutations that will become manifested in a generation or two because we are circumventing an evolutionarily important mechanism of genetic quality control. This needs to be investigated by genome sequencing.

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Drug may reduce female cancer patient infertility risk, according to study – Life Science Daily

Recommendation and review posted by sam

What’s Up with All the Zoo Babies? – Memphis Flyer (blog)

On Monday, the Memphis Zoo tweeted about their new baby flamingos the most recent in a long line of zoo babies we’ve met through the spring and summer.

Let’s see … there’s been Winnie the hippo, two giraffes, a sloth, an orangutan, rare Louisiana pine snakes, a Yellow-backed Duiker, aFrancois langur, and a Spot-nosed Guenon named Grommet.

So what is going on? Has there been extra-sexy time at the zoo? Do we need to have a birds-and-the-bees talk with them? Is this all a PR stunt?

Matt Thompson, director of the zoo’s Animal Programs, says that while springtime is a time for babies, reproduction at the zoo has been higher than average, and the push to get the public involved has also been higher than average.

The birth rate is all part of a bigger plan, bigger than the Memphis Zoo.

“Theres different programs for different species of animals Species Survival Plan (SSP),” Thompson explains. “For instance, there is a sloth SSP, and a hippo SSP and a giraffe SSP. What that is is a collection of zoo professionals, very smart people who analyze and look at the genetics of different lines of animals, so if the Memphis Zoo, for example, has a certain genetic line and a certain female that would really work well at the Indianapolis Zoo, they might put out a recommendation.They work their hardest to keep the gene pool healthy to prevent inbreeding and that kind of thing.”

A prime example of the SSP at work is one little hippo named Winnie.

“Her mother and father both came to us from Disneys Animal Kingdom and they came as a result of an SSP recommendation. It was kind of win-win because Disney was getting a little full with hippos as you can imagine, hippos take up a lot of room,” Thompson says. “We were building a new hippo exhibit and we needed a hippo or two, so we reached out to the SSP and they made recommendations based on genetics and thats how we wound up with these animals.”

As for birth control, Thompson says it ranges from oral contraceptives to physically pulling the animals apart. And there are accidents. “Sure, just like with people, there are surprises. Not many, but every now and then,” says Thompson.

Thompson says there are over 500 SSPs that cover all sorts of animals from pandas to lizards. The coordinator for the SSP for Louisiana Pine snakes, a rare species, is based at the Memphis Zoo.

Some of the toughest animals to breed are amphibians, and, yep, pandas.

“Its not for lack of trying,” Thompson says. “Pandas are challenging because they ovulate about once a year and you have about a three-day window for them to get pregnant. Theyve got to tell you when they are ready [and] thats very challenging.”

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What’s Up with All the Zoo Babies? – Memphis Flyer (blog)

Recommendation and review posted by simmons

Drug may curb female infertility from cancer treatments – Medical Xpress

A mouse ovary with proteins specific to oocytes labelled in red and yellow. The study reports that culturing such ovaries in the presence of a drug that inhibits DNA damage checkpoint enzymes protects the oocytes from lethal levels of radiation that would normally kill the entire oocyte reserve (small oocytes in picture). Credit: Schimenti Lab, Cornell University

An existing drug may one day protect premenopausal women from life-altering infertility that commonly follows cancer treatments, according to a new study.

Women who are treated for cancer with radiation or certain chemotherapy drugs are commonly rendered sterile. According to a 2006 study from Weill Cornell Medicine, nearly 40 percent of all female breast cancer survivors experience premature ovarian failure, in which they lose normal function of their ovaries and often become infertile.

Women are born with a lifetime reserve of oocytes, or immature eggs, but those oocytes are among the most sensitive cells in the body and may be wiped out by such cancer treatments.

The current study, published in the journal Genetics, was led by John Schimenti, Cornell University professor in the Departments of Biomedical Sciences and Molecular Biology and Genetics. The study builds on his 2014 research that identified a so-called checkpoint protein (CHK2) that becomes activated when oocytes are damaged by radiation.

CHK2 functions in a pathway that eliminates oocytes with DNA damage, a natural function to protect against giving birth to offspring bearing new mutations. When the researchers irradiated mice lacking the CHK2 gene, the oocytes survived, eventually repaired the DNA damage, and the mice gave birth to healthy pups.

The new study explored whether the checkpoint 2 pathway could be chemically inhibited.

“It turns out there were pre-existing CHK2 inhibitor drugs that were developed, ironically enough, for cancer treatment, but they turned out not to be very useful for treating cancer,” said Schimenti, the paper’s senior author. Vera Rinaldi, a graduate student in Schimenti’s lab, is the paper’s first author. “By giving mice the inhibitor drug, a small molecule, it essentially mimicked the knockout of the checkpoint gene,” Rinaldi said.

By inhibiting the checkpoint pathway, the oocytes were not killed by radiation and remained fertile, enabling birth of normal pups.

“The one major concern,” Schimenti said, “is that even though these irradiated oocytes led to the birth of healthy mouse pups, it’s conceivable that they harbor mutations that will become manifested in a generation or two, because we are circumventing an evolutionarily important mechanism of genetic quality control. This needs to be investigated by genome sequencing.”

When doctors recognize the need for oocyte-damaging cancer treatments, women may have their oocytes or even ovarian tissue removed and frozen, but this practice delays treatment. Also, when women run out of oocytes, women’s bodies naturally undergo menopause, as their hormonal systems shift.

“That is a serious dilemma and emotional issue,” Schimenti said, “when you layer a cancer diagnosis on top of the prospect of having permanent life-altering effects as a result of chemotherapy, and must face the urgent decision of delaying treatment to freeze oocytes at the risk of one’s own life.”

The study sets a precedent for co-administering this or related drugs and starting cancer therapy simultaneously, though such interventions would first require lengthy human trials.

“While humans and mice have different physiologies, and there is much work to be done to determine safe and effective dosages for people, it is clear that we have the proof of principle for this approach,” Schimenti said.

Explore further: Protein that culls damaged eggs identified, infertility reversed

Journal reference: Genetics

Provided by: Cornell University

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Drug may curb female infertility from cancer treatments – Medical Xpress

Recommendation and review posted by Bethany Smith

Fitness May Lower Breast Cancer Risk – New York Times

For the new study, which was published in July in Carcinogenesis, researchers at Colorado State University, Memorial Sloan Kettering Cancer Center in New York City and the University of Michigan opted to focus on breast cancer. Epidemiological studies have shown that being physically fit is associated with lower risk for the disease, but not why.

Because they wanted to examine the role of innate fitness in the disease, the scientists turned to a famous strain of rats bred by Lauren Koch and Steven Britton at the University of Michigan. Over multiple generations, these rats were tested on treadmills. Those that ran the farthest before tiring were subsequently mated with one another, while those that pooped out early likewise were paired up, until, ultimately, the pups displayed a large difference in inborn fitness.

The researchers used female pups born to mothers with either notably high or low aerobic capacity. These young animals did not exercise, so their fitness depended almost exclusively on genetics.

Before the pups reached puberty, they were exposed to a chemical known to be a potent breast cancer trigger. The researchers then checked them frequently for palpable tumors throughout adulthood. They also looked, after the animals deaths, for signs of malignancies that had been too small to feel and microscopically examined breast cells for various markers of cell health.

The differences between the animals with high and low fitness turned out to be striking. The rats with low natural fitness were about four times as likely to develop breast cancer as the rats with high fitness were, and showed more tumors once the disease began. They also tended to contract the disease earlier and continue to develop tumors later in life compared with highly fit rats.

The contrasts between the two types of rats continued deep inside their cells. The researchers found almost inverted relationships in how certain aspects of the cells worked, and in particular, in the operation of what is known as the mTOR network. Shorthand for mammalian target of rapamycin, the mTOR network is a group of interlinked proteins within a cell that sense how much energy is available, depending on levels of oxygen and other factors, and let the cell know if there is enough energy around for it to divide and replicate.

In the rats with high fitness in this study, the mTOR networks typically produced biochemical signals that tell cells to avoid dividing much, while in the rats with low fitness, the mTOR networks pumped out messages that would generally promote cell division. Unchecked cell division is a hallmark of cancer.

Past studies have noted that women with breast cancer often show hyperactive mTOR networks.

Of course, this study involved rats, which are not people. But the findings have potential relevance for us, says Henry J. Thompson, the director of the Cancer Prevention Lab at Colorado State University and the studys lead author.

The study underscores the pervasive effects of fitness on bodily health, he says. Even without exercise, the pups born with high fitness were remarkably resistant to breast cancer in this study, he says, and showed fine-tuned cell function.

Most of us are likely to be able to raise our particular innate fitness capacity with exercise, he says.

In future studies, he and his colleagues hope to use the Michigan rats to learn more about the precise types and amounts of exercise that might best augment fitness, especially in those born with low capacity, and the subsequent effects on cell health and cancer risk.

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Fitness May Lower Breast Cancer Risk – New York Times

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Kariba project 92pc complete – The Herald

Dr Undenge

From Walter Nyamukondiwa in KARIBAThe Kariba South Extension Project is now 92 percent complete and on course for commissioning by end of December as Government moves to clear the power deficit.

This is part of an eight-pronged approach to increasing power generation amid indications that about $500 million is being mobilised for the Hwange Life Extension project.

With a daily deficit of between 300MW and 600MW, the shortfall is being reduced progressively.In an interview on the sidelines of the Zimbabwe Institute of Engineers biennial congress here yesterday, Energy and Power Development Minister Dr Samuel Undenge hailed the collaboration between the contractors and Zesa management.

We are very pleased with the progress so far and to date we know that the Kariba South Extension Project is now 92 percent complete and everything is on course for its commissioning on 24 December, 2017, said Dr Undenge.

We applaud the focused work and effort that is being exhibited by the contractor (Sinohydro) and Zesa management that has seen so much progress.

He said initial challenges of foreign currency to pay suppliers were being overcome with the involvement of the Reserve Bank of Zimbabwe. The two new units will add a further 300MW to the national grid.

Zimbabwe has not had load-shedding for the last 20 months, as more than 300MW are being imported to offset the supply deficit.Expansion works and implementation of new projects ties in with regional efforts within SADC to offset the 8 247MW deficit.

This is largely due to lack of meaningful investment in power generation over the last two decades.Zimbabwes major investment in the power sector was in 1987 when Hwange Stage II was commissioned.

Dr Undenge said load-shedding is a major cost and inconvenience to consumers, undermines economic growth and suppresses foreign and local investment.The Hwange Life Extension seeks to recondition the power plant and add another 25 years to its productive life.

There are also plans to increase the thermal plants generation capacity from 550MW to 750MW.Government is implementing eight strategies including optimising existing generation plants, development of renewable energy and conservation among others.

This also includes guaranteeing production at Harare II and III (40MW), Bulawayo (25MW) and Munyati (30MW) thermal power stations.The Energy minister revealed that tendering for the Batoka Gorge South Bank which will add a further 1 400MW to the national grid will be out soon.

In terms of the Batoka Gorge project there are feasibility studies that have just been completed, then tenders will be send out. So that process is underway, said the Minister.

Other projects in the pipeline include the Devils Gorge (1 000MW), Hwange Western Area (1 200MW), Tokwe-Mukosi Hydro (15MW) and Gairezi Small Hydro (30MW).

Dr Undenge said the Minister of Finance and Economic Development Patrick Chinamasa was working on incentives to make investment into the energy sector attractive.

The Minister (Chinamasa) is trying to come up with a regime of incentives so that we make investment into the energy sector by private players more attractive. We need them to augment what Government is doing, said Minister Undenge.

Originally posted here:
Kariba project 92pc complete – The Herald

Recommendation and review posted by sam

Biopower in the Era of Biotech – lareviewofbooks


TWO TRENDS are on the rise, and one is about to make the other worse.

The first is epitomized in a July 2017 report in The Economist on the United Statess urban-rural divide, which noted that deaths of despair suicide, heart disease, and drug overdoses are increasing in the southeastern corner of West Virginia. Life expectancy for men is now 16.5 years lower than in neighboring Arlington. Christian H. Coopers moving essay in Nautilus entitled Why Poverty Is Like a Disease, Karin Goodwins journalism in the Guardian, and James Bloodworths op-ed in New Scientist have piled on additional accounts of how chronic stress and loss of a sense of control can be our undoing.

Meanwhile, in the second trend, biotechs rise, ever more powerful tools are being developed for in vitro fertilization, and for anti-aging and cancer technologies. Some of the latter run to six figures, which means some insurance companies may not cover them.

As economist Thomas Piketty noted in 2014, and so many have since Trumps election, the United States is embroiled in an intensifying era of class struggle, which expresses itself not only in differential impacts on health as pegged to class, but also in the growing unlikelihood that the rural poor, and indeed the poor in general, can securely provide for their children, no doubt a factor in the declining fertility rate. At the same time, the commercialization of science steadily escalates, along with its corollary: the commercialization of human life. Many life scientists hope to start a company and strike it rich. Many have. Entrepreneurial scientists now count themselves among the wealthiest of Americans, and, as the market so freely allows, some of them build their careers on the development and sale of biotech solutions. Offering a route to positive eugenics, longer life, and interventions into deadly diseases, these life-saving and life-enhancing technologies will assuredly widen the public health gap.

First, consider birth. In December 2015, I attended a meeting at the National Academy of Sciences in which a member of the American Society of Reproductive Medicine stood up to proclaim that parents have a right to use the gene-editing tool CRISPR-Cas9 and in vitro, or IVF, technologies to have a genetically connected child. These technologies could be used, he explained, to repair the code for deleterious genes that run in certain families or improve older parents chances of a birth. Bioethicist Hille Haker argued that there is a difference between a negative right, which is a freedom from harm or tyranny, and a full positive right, which is a freedom to access potential benefits. Having a healthy child is a negative right, according to Haker, meaning a right you have unless someone (such as the Chinese government) takes it away, but not a full positive right. If it were a full positive right, society would be hidebound in debt to pay for each of its citizens to have children, applying genetic tests and in vitro techniques as needed. Almost no one would contend that society has such a responsibility, she argued. You may disagree with me, but as an ethicist I put the consequential assessment in terms of rights and obligations, Haker said. There is no right to a genetically related child, it is a high value, not a right.

In August, Shoukhrat Mitalipov, at the Oregon Health & Science University in Portland,controversially became the first scientist in the United States to use the gene modification system CRISPR to alter a human embryo. He modified the gene MYBPC3; when mutated in a single copy of that gene, it can increase your risk for a rare heart condition. Forty-two of the 58 embryos he altered, or 72 percent, had two mutation-free copies of the gene in every cell, and, most importantly, there were no unintended mutations. This study suggests that any technical limitations will soon be overcome, which will then open up a landslide of ethical questions related to equity. Keep in mind that many of us carry a genetic variant that predicts risk for a serious condition. Will insurance companies pay for these gene modifications, and to what extent? Or will the wealthy alone be able to afford to modify their embryos?

This past winter, the National Academy of Sciences and National Academy of Medicine published a report entitled Human Genome Editing: Science, Ethics, and Governance that signals support for gene editing to the heritable, or germline, code, but only in cases where no safer options are available. In her book, A Crack in Creation, Jennifer Doudna, one of the inventors of CRISPR-Cas9, also signaled her openness to CRISPR-ized babies through gene modification.

Already, insurance coverage of in vitro fertilization varies widely by state, and now gene modification techniques may further challenge the concept of what is medically necessary. A mutated APP gene can predict early-onset Alzheimers. A mutated BRCA gene can predict breast or ovarian cancer. A disrupted PCSK9 can lower LDL cholesterol. The Food and Drug Administration actually thinks of CRISPR as a drug rather than a device, so in the United States, CRISPR must pass through a regulatory process for each target it modifies, even in an embryo. For some single-gene or Mendelian diseases such as Tay-Sachs and cystic fibrosis, or the immune disorders NEMO or X-SCID, CRISPR technology could be a fairly straightforward new treatment modality in vitro. Keep in mind, however, that generating an embryo without a heritable mutation can, in the vast majority of cases, already be accomplished by screening embryos before implantation. This raises the question of when CRISPR would be indispensable. In fact, genetic variants in BRCA, which tend to run in high-risk families, are nested in complex so-called epistatic relationships involving the interaction of multiple genetic variants. It would be impossible to know whether altering that single gene reduces cancer in a family in future generations. And if it did, would poor families be able to afford it? Probably not.

Marcy Darnovsky, director of the Center for Genetics and Society in Berkeley, California,and her team have counted as many as 45 countries that ban germline modification. The United States is not one of them, and instead it handles germline editing in vitro much as it does stem cell research by prohibiting funding to scientists to do this research and prohibiting funding to the FDA to review applications for clinical trials of CRISPR babies. We can be sure that entrepreneurial scientists who stand to cash in on such technologies are working to alter such policies. Using gene-editing techniques in a test tube is arguably safer than using gene modification techniques on a living person in a test tube, youre modifying a clump of 64 cells or fewer, rather than trillions of cells, and eliminating the risk of an immune reaction. But those test tube techniques still require genetic diagnostics to know something about a familys risk, not to mention requiring the capital outlay to pay for expensive genetic diagnosis and IVF treatments in short, not particularly realistic or affordable for most of us.

Ultimately, none of this would help living people who develop a disease such as cancer. New technologies such as genetically engineered T-cells combined with CRISPR will enable doctors to coax the bodys immune system into fighting cancer,the first of which wasapprovedonAugust 30, which Novartis will sell in the U.S. for$475,000, a drug price that is nine times the median income in the United States. This means that high-cost medicines will create wealthy scientists and just as surely will exacerbate the health divide. This may be the reality if the Trump administration repeals the Affordable Care Act, but it may also be the reality in a single-payer system such as the National Health Service in Britain, which isnt prepared to pay for these high-priced medicines either. Indeed, oncologist and author Siddhartha Mukherjee warned this summer at the annual American Society of Clinical Oncology meeting about dividing the world into the rich who can afford personalized cancer treatment and the poor who cannot. If health insurance is unequal or inadequate, the only solution may be to use the power of the state to regulate the cost of cancer drugs. A drug price fairness initiative is in fact already on the ballot in Ohio; and transparency laws, established in Vermont, are clarifying their cost. We may have to cap them by executive order.

In the 1970s, Michel Foucault developed the influential notions of biopower and biopolitics, which gave power its access even to the body. In his words, biopolitics is the endeavour, begun in the eighteenth century, to rationalize problems presented to governmental practice by the phenomena characteristic of a group of living human beings constituted as a population: health, sanitation, birth rate, longevity, race. He defines biopower as the techniques for achieving the subjugation of bodies and the control of populations. But even Foucault had yet to conceive of how new biotechnologies could be leveraged. The industrial revolution of the human genome initiates an era in which social divisions are amplified by means of genomics technologies.

Foucault was wrong about some things, such as health and mental illness being solely the result of social forces. But he may have been only partially wrong. As neuroscientist Robert Sapolsky and so many others have noted, stress is distributed unequally across the social spectrum. Hierarchies of wealth and power institutionalize certain forms of stress, including chronic forms, and, according to a spate of recent research, social hierarchies are then embedded in body chemistry through social imprinting. If this research holds up, then it seems clear that we cant undo the damages accrued by years of poverty or poor social status by giving more funding to wealthy scientists. Theres been a clear shift to funding genetics research into mental illness, but the fact is that this research supports the drug-maker model, which then mostly benefits those who control and sell those drugs. It supports their careers through generous amounts of public funding. It does not support the disenfranchised who may need more than drug-based interventions.

The philosopher Nick Bostrom defines transhumanism as the doctrine that

holds that current human nature is improvable through the use of applied science and other rational methods, which may make it possible to increase human health-span, extend our intellectual and physical capacities, and give us increased control over our own mental states and moods.

This not-so-subtle movement includes efforts by the National Institute of Mental Health to monetize the field of psychiatry by basing research on a molecular biomarker or gene target that can be pursued as a diagnostic test or drug target, an agenda that is, in fact, now in retreat because so few reliable biomarkers or targets have actually been discovered. Clinical biomarkers and biochemical transformations have failed to make a dent in suicide rates, not to mention in the incident rates or prognosis of serious psychiatric ills. The most promising discovery coming out of research into psychiatric drugs in recent years may be a street drug called ketamine, or Special K, a worldly knowledge that experts have expropriated from regular folks.

As for the budding life-extension industry, it is built around over-the-counter drugs, such as nicotinamide mononucleotide (NMN), and the development of new drugs to degrade proteins that build up in brains and are associated with age-related diseases such as Alzheimers and Parkinsons disease. In 2013, the Time magazine cover story Can Google Solve Death? became part of the transhumanist spectacle when it noted that, for CEO Larry Page, solving cancer may not be a big enough task. The article introduced life extension company Calico, which is currently working on ways to degrade proteins that build up in the brain and are correlated with age-related diseases. But insurers may not have an incentive to pay for life-extension techniques that add bonus years, since insurance is more costly when we are older. As a result, these pursuits only contribute to the trope that life extension is a luxury pursued by wealthy Silicon Valley entrepreneurs stymied by their own loss of control. The most potent real news is precisely the connection between income and longevity. In short: The fact that such studies have led to no major societal shifts in how we value life suggests that the longevity that drug makers pursue as a financial prospect is solely about extending life for the wealthy.

An urgent question, therefore, is the following: Are our scientific institutions working on behalf of the public and fairness, and so of distributive justice, or are they working for commercial interests? And another disturbing question: Are these interests being normalized before we can even debate them? The fact that scientists themselves like to appeal to economic interests when asking for public funding should offer one clue. And of course it doesnt help that scientists want to sell us stuff.

In the famous 1971 Chomsky-Foucault Debate, Foucault argued that those who take up social justice causes are in fact doing so only because they want to take power. Chomsky demurred:

I think its too hasty to characterize our existing systems of justice as merely systems of class oppression [] they also embody a kind of groping towards the true humanly valuable concepts of justice and decency and love and kindness and sympathy, which I think are real.

Of course, institutions can be applied to advance justice and fairness, or be exploited for special interests. If authority is broadly distributed and innate to the wellsprings of the mind, then institutions are an extension of principles that reside within us and should seek to ensure access and fairness. But if scientists are working toward selling biotech solutions at the highest price the market will allow, then scientific institutions may be exploited for power and profit and thats just capitalism.

The irony is that we may need the state to ensure fair access to medicines we fund, and to prohibit genetic enhancement or reproductive advantages if all of us cant afford or access them. This is no small problem. Political scientist Francis Fukuyama called transhumanism the worlds most dangerous idea, suggesting that the commercialization of biotech would create increasing unfairness. In his book Our Posthuman Future, he qualifies his original end of history thesis, arguing that human genetic engineering and in vitro fertilization might perpetuate social divisions, putting liberal democracy at risk. If there is one imperial power left on the world stage, Fukuyama argues, it is biotech. What should we do in response to biotechnology that in the future will mix great potential benefits with threats that are either physical and overt or spiritual and subtle? he asks. The answer is obvious: We should use the power of the state to regulate it.

Here are some recommendations: the price of biologic medicines (gene and cell therapies) should be fixed or capped that is, if the public is expected to subsidize their cost through National Institutes of Health funding. If that sounds too much like socialism, then we need to stop socializing the costs and risks of drug development through NIH funding. A second point: The federal legislators and the FDA should have strong regulatory control over the creation of gene modifications to the heritable code of newborns. For the moment, they are able to constrain those enterprises as mentioned earlier, the FDA regulates gene modifications as a drug, and any specific target must pass through an extensive regulatory process. Once approved, then some sort of public insurance must make them accessible to everyone, or else biotech will assuredly exacerbate social and economic inequality, thus affecting the Freedom Index in the United States.

Scientists are readily using taxpayer funding to advance their own economic interests, thereby institutionalizing power and wealth. Indeed, many managerial scientists count themselves among the wealthiest Americans with annual salaries in the six and seven figures. If the state has a role, it is to live up to the ideals which we are groping towards, the concepts of justice and decency, rather than the current reality of scientific institutions seeding biotech startups. The fact is that scientists are increasingly testing public trust. Whether they should continue to receive tax-exempt funding ought to depend on whether they are working toward fair and equal access to medicine, lest by the time science funding reaches a commercial shelf, life is simply up for sale.

Jim Kozubek is the author ofModern Prometheus: Editing the Human Genome withCrispr-Cas9,published by the Cambridge University Press.

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Biopower in the Era of Biotech – lareviewofbooks

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Beware of the Overstated Service Life in the Cost Approach – Lexology (registration)

The cost approach requires the identity and quantification of three types of obsolescence physical, functional and economic. Assessors frequently account only for physical depreciation (although some assessors/appraisers apply a special factor in an attempt to capture functional and economic obsolescence). Physical depreciation is dependent upon accurately determining: (1) the effective age, which is the chronological age or the weighted chronological age (if physical improvements have been made) adjusted for physical condition; and (2) the appropriate service life of the facility (some also measure and apply remaining life). Needless to say, an assessor/appraiser can increase a propertys value by misstating any one of these factors. So, the taxpayer must closely review the assessment process to make sure that each factor reflects market realities and the facilitys physical condition. It is also essential that the assessor/appraiser apply an appropriate service life that considers the major components of the facility and their interaction on the life of the facility. A purchaser of the building only recognizes value to the extent that the building can continue to produce profitable net operating income at a required rate of return. An example is an old K Mart or Sears building. Physically, for retail purposes, they are likely to have short term life, as major reparations are likely necessary to make the facilities operable in todays demanding retail environment. Nonetheless, taxing jurisdictions often apply longer physical lives that are based on the effect of such reparations (i.e., life extension); even though, they have not yet been incurred and without accounting for their cost. This artificially boosts the facilitys valuation.

Bottom line, if the taxpayer does not accurately identify and quantify the physical age, condition and service life, its property will continue to be over valued by the assessor/appraiser. If economic life is applied, the appraiser needs to recognize and quantify the other non-physical forms of obsolescence captured in the economic life to avoid double counting.

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Beware of the Overstated Service Life in the Cost Approach – Lexology (registration)

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‘America’s Tall Ship’ – Virginia Connection Newspapers

The U.S. Coast Guard Cutter Eagle moors at Point Lumley Park in Old Town Sept. 4, marking the first time in 11 years that the vessel known as Americas Tall Ship returned to the Washington area.

Alexandria For the first time in 11 years, the U.S. Coast Guard Cutter Eagle arrived in the

Washington area, mooring at Old Towns Point Lumley Park Sept. 4 as part of the tall ships summer deployment.

Also known as Americas Tall Ship, Eagle is the largest tall ship flying the U.S. flag and the only active commissioned sailing vessel in American military service. Eagle is the only square-rigger in the U.S. military services and is used to train students at the U.S. Coast Guard Academy in New London, Conn.

The Eagle has a fascinating history, said Old Town resident Hal Hardaway after touring the vessel Sept. 5. Eagle was hull #508 built in the Blohm and Voss shipyard in Hamburg in 1936. That yards next hull # 509 was Bismark.

Alexandria is Eagle’s final stop in its summer deployment, which has spanned

five months and included 14 ports, including multiple ports along the Eastern Seaboard, Canada and Bermuda.

Also known as the Coast Guard Barque Eagle, the ship left Baltimore April 26 bound for New London to commence the 2017 cadet summer training program. Eagle and her crew, including Capt. Matthew Meilstrup as commanding officer, have been at the Coast Guard Yard facility in Baltimore as part of a Service Life Extension Project that will keep the ship away from its home port of New London for several years.

The ship was built in 1936 in Germany and commissioned as Horst Wessel, one of three sail training ships operated by the pre-World War II German navy. At the close of World War II, Horst Wessel was taken as a war reparation by the United States, recommissioned as the U.S. Coast Guard Cutter Eagle and sailed to New London. The vessel is used for at-sea leadership and professional development training for future officers of the U.S. Coast Guard.

Eagle is scheduled to depart Point Lumley at approximately 4:30 a.m. Sept. 8. The Woodrow Wilson Bridge span will be raised at that time to allow Eagle to sail through as it makes its return to Baltimore.

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‘America’s Tall Ship’ – Virginia Connection Newspapers

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The Promise of Induced Pluripotent Stem Cells (iPSCs …

Charles A. Goldthwaite, Jr., Ph.D.

In 2006, researchers at Kyoto University in Japan identified conditions that would allow specialized adult cells to be genetically “reprogrammed” to assume a stem cell-like state. These adult cells, called induced pluripotent stem cells (iPSCs), were reprogrammed to an embryonic stem cell-like state by introducing genes important for maintaining the essential properties of embryonic stem cells (ESCs). Since this initial discovery, researchers have rapidly improved the techniques to generate iPSCs, creating a powerful new way to “de-differentiate” cells whose developmental fates had been previously assumed to be determined.

Although much additional research is needed, investigators are beginning to focus on the potential utility of iPSCs as a tool for drug development, modeling of disease, and transplantation medicine. The idea that a patient’s tissues could provide him/ her a copious, immune-matched supply of pluripotent cells has captured the imagination of researchers and clinicians worldwide. Furthermore, ethical issues associated with the production of ESCs do not apply to iPSCs, which offer a non-controversial strategy to generate patient-specific stem cell lines. As an introduction to this exciting new field of stem cell research, this chapter will review the characteristics of iPSCs, the technical challenges that must be overcome before this strategy can be deployed, and the cells’ potential applications to regenerative medicine.

As noted in other chapters, stem cells represent a precious commodity. Although present in embryonic and adult tissues, practical considerations such as obtaining embryonic tissues and isolating relatively rare cell types have limited the large-scale production of populations of pure stem cells (see the Chapter, “Alternate Methods for Preparing Pluripotent Stem Cells” for details). As such, the logistical challenges of isolating, culturing, purifying, and differentiating stem cell lines that are extracted from tissues have led researchers to explore options for “creating” pluripotent cells using existing non-pluripotent cells. Coaxing abundant, readily available differentiated cells to pluripotency would in principle eliminate the search for rare cells while providing the opportunity to culture clinically useful quantities of stem-like cells.

One strategy to accomplish this goal is nuclear reprogramming, a technique that involves experimentally inducing a stable change in the nucleus of a mature cell that can then be maintained and replicated as the cell divides through mitosis. These changes are most frequently associated with the reacquisition of a pluripotent state, thereby endowing the cell with developmental potential. The strategy has historically been carried out using techniques such as somatic cell nuclear transfer (SCNT),1,2 altered nuclear transfer (ANT),3,4 and methods to fuse somatic cells with ESCs5,6 (see “Alternate Methods for Preparing Pluripotent Stem Cells” for details of these approaches). From a clinical perspective, these methods feature several drawbacks, such as the creation of an embryo or the development of hybrid cells that are not viable to treat disease. However, in 2006, these efforts informed the development of nuclear reprogramming in vitro, the breakthrough method that creates iPSCs.

This approach involves taking mature “somatic” cells from an adult and introducing the genes that encode critical transcription factor proteins, which themselves regulate the function of other genes important for early steps in embryonic development (See Fig. 10.1). In the initial 2006 study, it was reported that only four transcription factors (Oct4, Sox2, Klf4, and c-Myc) were required to reprogram mouse fibroblasts (cells found in the skin and other connective tissue) to an embryonic stem celllike state by forcing them to express genes important for maintaining the defining properties of ESCs.7 These factors were chosen because they were known to be involved in the maintenance of pluripotency, which is the capability to generate all other cell types of the body. The newly-created iPSCs were found to be highly similar to ESCs and could be established after several weeks in culture.7,8 In 2007, two different research groups reached a new milestone by deriving iPSCs from human cells, using either the original four genes9 or a different combination containing Oct4, Sox2, Nanog, and Lin28.10 Since then, researchers have reported generating iPSCs from somatic tissues of the monkey11 and rat.12,13

However, these original methods of reprogramming are inefficient, yielding iPSCs in less than 1% of the starting adult cells.14,15 The type of adult cell used also affects efficiency; fibroblasts require more time for factor expression and have lower efficiency of reprogramming than do human keratinocytes, mouse liver and stomach cells, or mouse neural stem cells.1419

Several approaches have been investigated to improve reprogramming efficiency and decrease potentially detrimental side effects of the reprogramming process. Since the retroviruses used to deliver the four transcription factors in the earliest studies can potentially cause mutagenesis (see below), researchers have investigated whether all four factors are absolutely necessary. In particular, the gene c-Myc is known to promote tumor growth in some cases, which would negatively affect iPSC usefulness in transplantation therapies. To this end, researchers tested a three-factor approach that uses the orphan nuclear receptor Esrrb with Oct4 and Sox2, and were able to convert mouse embryonic fibroblasts to iPSCs.20 This achievement corroborates other reports that c-Myc is dispensable for direct reprogramming of mouse fibroblasts.21 Subsequent studies have further reduced the number of genes required for reprogramming,2226 and researchers continue to identify chemicals that can either substitute for or enhance the efficiency of transcription factors in this process.27 These breakthroughs continue to inform and to simplify the reprogramming process, thereby advancing the field toward the generation of patient-specific stem cells for clinical application. However, as the next section will discuss, the method by which transcription factors are delivered to the somatic cells is critical to their potential use in the clinic.

Figure 10.1. Generating Induced Pluripotent Stem Cells (iPSCs).

2008 Terese Winslow

Reprogramming poses several challenges for researchers who hope to apply it to regenerative medicine. To deliver the desired transcription factors, the DNA that encodes their production must be introduced and integrated into the genome of the somatic cells. Early efforts to generate iPSCs accomplished this goal using retroviral vectors. A retrovirus is an RNA virus that uses an enzyme, reverse transcriptase, to replicate in a host cell and subsequently produce DNA from its RNA genome. This DNA incorporates into the host’s genome, allowing the virus to replicate as part of the host cell’s DNA. However, the forced expression of these genes cannot be controlled fully, leading to unpredictable effects.28 While other types of integrating viruses, such as lentiviruses, can increase the efficiency of reprogramming,16 the expression of viral transgenes remains a critical clinical issue. Given the dual needs of reducing the drawbacks of viral integration and maximizing reprogramming efficiency, researchers are exploring a number of strategies to reprogram cells in the absence of integrating viral vectors2730 or to use potentially more efficient integrative approaches.31,32

Before reprogramming can be considered for use as a clinical tool, the efficiency of the process must improve substantially. Although researchers have begun to identify the myriad molecular pathways that are implicated in reprogramming somatic cells,15 much more basic research will be required to identify the full spectrum of events that enable this process. Simply adding transcription factors to a population of differentiated cells does not guarantee reprogrammingthe low efficiency of reprogramming in vitro suggests that additional rare events are necessary to generate iPSCs, and the efficiency of reprogramming decreases even further with fibroblasts that have been cultured for long time periods.33 Furthermore, the differentiation stage of the starting cell appears to impact directly the reprogramming efficiency; mouse hematopoietic stem and progenitor cells give rise to iPSCs up to 300 times more efficiently than do their terminally-differentiated B- and T-cell counterparts.34 As this field continues to develop, researchers are exploring the reprogramming of stem or adult progenitor cells from mice24,25,34,35 and humans23,26 as one strategy to increase efficiency compared to that observed with mature cells.

As these discussions suggest, clinical application of iPSCs will require safe and highly efficient generation of stem cells. As scientists increase their understanding of the molecular mechanisms that underlie reprogramming, they will be able to identify the cell types and conditions that most effectively enable the process and use this information to design tools for widespread use. Clinical application of these cells will require methods to reprogram cells while minimizing DNA alterations. To this end, researchers have found ways to introduce combinations of factors in a single viral “cassette” into a known genetic location.36 Evolving tools such as these will enable researchers to induce programming more safely, thereby informing basic iPSC research and moving this technology closer to clinical application.

ESCs and iPSCs are created using different strategies and conditions, leading researchers to ask whether the cell types are truly equivalent. To assess this issue, investigators have begun extensive comparisons to determine pluripotency, gene expression, and function of differentiated cell derivatives. Ultimately, the two cell types exhibit some differences, yet they are remarkably similar in many key aspects that could impact their application to regenerative medicine. Future experiments will determine the clinical significance (if any) of the observed differences between the cell types.

Other than their derivation from adult tissues, iPSCs meet the defining criteria for ESCs. Mouse and human iPSCs demonstrate important characteristics of pluripotent stem cells, including expressing stem cell markers, forming tumors containing cell types from all three primitive embryonic layers, and displaying the capacity to contribute to many different tissues when injected into mouse embryos at a very early stage of development. Initially, it was unclear that iPSCs were truly pluripotent, as early iPSC lines contributed to mouse embryonic development but failed to produce live-born progeny as do ESCs. In late 2009, however, several research groups reported mouse iPSC lines that are capable of producing live births,37,38 noting that the cells maintain a pluripotent potential that is “very close to” that of ESCs.38 Therefore, iPSCs appear to be truly pluripotent, although they are less efficient than ESCs with respect to differentiating into all cell types.38 In addition, the two cell types appear to have similar defense mechanisms to thwart the production of DNA-damaging reactive oxygen species, thereby conferring the cells with comparable capabilities to maintain genomic integrity.39

Undifferentiated iPSCs appear molecularly indistinguishable from ESCs. However, comparative genomic analyses reveal differences between the two cell types. For example, hundreds of genes are differentially expressed in ESCs and iPSCs,40 and there appear to be subtle but detectable differences in epigenetic methylation between the two cell types.41,42 Genomic differences are to be expected; it has been reported that gene-expression profiles of iPSCs and ESCs from the same species differ no more than observed variability among individual ESC lines.43 It should be noted that the functional implications of these findings are presently unknown, and observed differences may ultimately prove functionally inconsequential.44

Recently, some of the researchers who first generated human iPSCs compared the ability of iPSCs and human ESCs to differentiate into neural cells (e.g., neurons and glia).45 Their results demonstrated that both cell types follow the same steps and time course during differentiation. However, although human ESCs differentiate into neural cells with a similar efficiency regardless of the cell line used, iPSC-derived neural cells demonstrate lower efficiency and greater variability when differentiating into neural cells. These observations occurred regardless of which of several iPSC-generation protocols were used to reprogram the original cell to the pluripotent state. Experimental evidence suggests that individual iPSC lines may be “epigenetically unique” and predisposed to generate cells of a particular lineage. However, the authors believe that improvements to the culturing techniques may be able to overcome the variability and inefficiency described in this report.

These findings underpin the importance of understanding the inherent variability among discrete cell populations, whether they are iPSCs or ESCs. Characterizing the variability among iPSC lines will be crucial to apply the cells clinically. Indeed, the factors that make each iPSC line unique may also delay the cells’ widespread use, as differences among the cell lines will affect comparisons and potentially influence their clinical behavior. For example, successfully modeling disease requires being able to identify the cellular differences between patients and controls that lead to dysfunction. These differences must be framed in the context of the biologic variability inherent in a given patient population. If iPSC lines are to be used to model disease or screen candidate drugs, then variability among lines must be minimized and characterized fully so that researchers can understand how their observed results match to the biology of the disease being studied. As such, standardized assays and methods will become increasingly important for the clinical application of iPSCs, and controls must be developed that account for variability among the iPSCs and their derivatives.

Additionally, researchers must understand the factors that initiate reprogramming towards pluripotency in different cell types. A recent report has identified one factor that initiates reprogramming in human fibroblasts,46 setting the groundwork for developing predictive models to identify those cells that will become iPSCs. An iPSC may carry a genetic “memory” of the cell type that it once was, and this “memory” will likely influence its ability to be reprogrammed. Understanding how this memory varies among different cell types and tissues will be necessary to reprogram successfully.

iPSCs have the potential to become multipurpose research and clinical tools to understand and model diseases, develop and screen candidate drugs, and deliver cell-replacement therapy to support regenerative medicine. This section will explore the possibilities and the challenges that accompany these medical applications, with the caveat that some uses are more immediate than others. For example, researchers currently use stem cells to test/screen drugs or as study material to identify molecules or genes implicated in regeneration. Conducting experiments or testing candidate drugs on human cells grown in culture enables researchers to understand fundamental principles and relationships that will ultimately inform the use of stem cells as a source of tissue for transplantation. Therefore, using iPSCs in cell-replacement therapies is a future application of these cells, albeit one that has tremendous clinical potential. The following discussion will highlight recent efforts toward this goal while recognizing the challenges that must be overcome for these cells to reach the clinic.

Reprogramming technology offers the potential to treat many diseases, including Alzheimer’s disease, Parkinson’s disease, cardiovascular disease, diabetes, and amyotrophic lateral sclerosis (ALS; also known as Lou Gehrig’s disease). In theory, easily-accessible cell types (such as skin fibroblasts) could be biopsied from a patient and reprogrammed, effectively recapitulating the patient’s disease in a culture dish. Such cells could then serve as the basis for autologous cell replacement therapy. Because the source cells originate within the patient, immune rejection of the differentiated derivatives would be minimized. As a result, the need for immunosuppressive drugs to accompany the cell transplant would be lessened and perhaps eliminated altogether. In addition, the reprogrammed cells could be directed to produce the cell types that are compromised or destroyed by the disease in question. A recent experiment has demonstrated the proof of principle in this regard,47 as iPSCs derived from a patient with ALS were directed to differentiate into motor neurons, which are the cells that are destroyed in the disease.

Although much additional basic research will be required before iPSCs can be applied in the clinic, these cells represent multi-purpose tools for medical research. Using the techniques described in this article, researchers are now generating myriad disease-specific iPSCs. For example, dermal fibroblasts and bone marrow-derived mesencyhmal cells have been used to establish iPSCs from patients with a variety of diseases, including ALS, adenosine deaminase deficiency-related severe combined immunodeficiency, Shwachman- Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophies, Parkinson’s disease, Huntington’s disease, type 1 diabetes mellitus, Down syndrome/trisomy 21, and spinal muscular atrophy.4749 iPSCs created from patients diagnosed with a specific genetically-inherited disease can then be used to model disease pathology. For example, iPSCs created from skin fibroblasts taken from a child with spinal muscular atrophy were used to generate motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother.48 As iPSCs illuminate the development of normal and disease-specific pathologic tissues, it is expected that discoveries made using these cells will inform future drug development or other therapeutic interventions.

One particularly appealing aspect of iPSCs is that, in theory, they can be directed to differentiate into a specified lineage that will support treatment or tissue regeneration. Thus, somatic cells from a patient with cardiovascular disease could be used to generate iPSCs that could then be directed to give rise to functional adult cardiac muscle cells (cardiomyocytes) that replace diseased heart tissue, and so forth. Yet while iPSCs have great potential as sources of adult mature cells, much remains to be learned about the processes by which these cells differentiate. For example, iPSCs created from human50 and murine fibroblasts5153 can give rise to functional cardiomyocytes that display hallmark cardiac action potentials. However, the maturation process into cardiomyocytes is impaired when iPSCs are usedcardiac development of iPSCs is delayed compared to that seen with cardiomyocytes derived from ESCs or fetal tissue. Furthermore, variation exists in the expression of genetic markers in the iPSC-derived cardiac cells as compared to that seen in ESC-derived cardiomyocytes. Therefore, iPSC-derived cardiomyocytes demonstrate normal commitment but impaired maturation, and it is unclear whether observed defects are due to technical (e.g., incomplete reprogramming of iPSCs) or biological barriers (e.g., functional impairment due to genetic factors). Thus, before these cells can be used for therapy, it will be critical to distinguish between iPSC-specific and disease-specific phenotypes.

However, it must be noted that this emerging field is continually evolving; additional basic iPSC research will be required in parallel with the development of disease models. Although the reprogramming technology that creates iPSCs is currently imperfect, these cells will likely impact future therapy, and “imperfect” cells can illuminate many areas related to regenerative medicine. However, iPSC-derived cells that will be used for therapy will require extensive characterization relative to what is sufficient to support disease modeling studies. To this end, researchers have begun to use imaging techniques to observe cells that are undergoing reprogramming to distinguish true iPSCs from partially-reprogrammed cells.54 The potential for tumor formation must also be addressed fully before any iPSC derivatives can be considered for applied cell therapy. Furthermore, in proposed autologous therapy applications, somatic DNA mutations (e.g., non-inherited mutations that have accumulated during the person’s lifetime) retained in the iPSCs and their derivatives could potentially impact downstream cellular function or promote tumor formation (an issue that may possibly be circumvented by creating iPSCs from a “youthful” cell source such as umbilical cord blood).55 Whether these issues will prove consequential when weighed against the cells’ therapeutic potential remains to be determined. While the promise of iPSCs is great, the current levels of understanding of the cells’ biology, variability, and utility must also increase greatly before iPSCs become standard tools for regenerative medicine.

Since their discovery four years ago, induced pluripotent stem cells have captured the imagination of researchers and clinicians seeking to develop patient-specific therapies. Reprogramming adult tissues to embryonic-like states has countless prospective applications to regenerative medicine, drug development, and basic research on stem cells and developmental processes. To this point, a PubMed search conducted in April 2010 using the term “induced pluripotent stem cells” (which was coined in 2006) returned more than 1400 publications, indicating a highly active and rapidlydeveloping research field.

However, many technical and basic science issues remain before the promise offered by iPSC technology can be realized fully. For putative regenerative medicine applications, patient safety is the foremost consideration. Standardized methods must be developed to characterize iPSCs and their derivatives. Furthermore, reprogramming has demonstrated a proof of-principle, yet the process is currently too inefficient for routine clinical application. Thus, unraveling the molecular mechanisms that govern reprogramming is a critical first step toward standardizing protocols. A grasp on the molecular underpinnings of the process will shed light on the differences between iPSCs and ESCs (and determine whether these differences are clinically significant). Moreover, as researchers delve more deeply into this field, the effects of donor cell populations can be compared to support a given application; i.e., do muscle-derived iPSCs produce more muscle than skin-derived cells? Based on the exciting developments in this area to date, induced pluripotent stem cells will likely support future therapeutic interventions, either directly or as research tools to establish novel models for degenerative disease that will inform drug development. While much remains to be learned in the field of iPSC research, the development of reprogramming techniques represents a breakthrough that will ultimately open many new avenues of research and therapy.

Chapter 9|Table of Contents|Chapter 11

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The Promise of Induced Pluripotent Stem Cells (iPSCs …

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New gene editing tech promises to be even better than CRISPR – Digital Trends

Markets Insider
New gene editing tech promises to be even better than CRISPR
Digital Trends
Just when we were getting used to the CRISPR/Cas9 gene editing revolution, a new fourth-generation DNA base editor has come along.
University of South Carolina to provide Transomic Technologies …Markets Insider

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New gene editing tech promises to be even better than CRISPR – Digital Trends

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Artis funds Excision to test whether CRISPR can cure HIV … – FierceBiotech

Excision BioTherapeutics has raised money to move what it sees as a cure for HIV into the clinic. Stemcentrx backer Artis Ventures led the $10 million seed round to equip Excision to start human testing of its CRISPR-enabled attack on latent HIV virus.

Philadelphia-based Excision is built on research conducted at Temple Universitys Lewis Katz School of Medicine. The work led to a paper published last year, in which Excision co-founder Kamel Khalili, Ph.D., and his partners administered a multiplex of guide RNAs (gRNAs) and Staphylococcus aureus Cas9 to HIV-infected mice. The team designed the treatment to remove a large, essential DNA fragment from HIV.

Results from the study furthered Excisions belief its candidate can wipe out HIV provirus from all tissues in the body without causing genotoxic effects and off-target editing.

That belief prompted the founding of Excision in 2015. Having generated animal data to back up the belief, Excision has high hopes for the approach.

We’re in this to cure patients of HIV, Excision CEO Thomas Malcolm, Ph.D., said.

Excision sees an HIV CRISPR Cas9/gRNA multiplex biologic based on Khalilis workEBT101as its best shot of meeting this lofty goal. The plan is to wrap up IND-enabling studies of the candidate in the months to come and get it into the clinic around the end of next year. That small trial will act as an early test of the safety and, to a lesser extent, the efficacy of EBT101 and its delivery system.

Some of Khalilis projects used adeno-associated virus (AAV) vectors to deliver sgRNAs and Cas9. But Excision is now looking at a lentiviral approach.

It’s really more specific for the types of cells that have that latent virus. HIV itself is a lentivirus so it makes sense to use a lentiviral shell to deliver the therapeutic, Malcolm said. Were showing we can easily access all of these reservoirs with this approach.

The plan for later trials is to use EBT101 to target these reservoirs in patients taking cocktails of HIV inhibitors to control the virus. These cocktails, such as Gileads Genvoya, lower HIV viral loads to undetectable levels in most patients. But, while that has improved outcomes significantly, Excision is confident a product that eradicates the virus would still find a market.

This confidence is based on what Malcolm calls the baggage that comes with cocktails. That term covers the risk of noncompliance to the daily treatment regimen and the comorbidities common in people who live with HIV, although there is evidence suggesting treatment with modern antiretroviral therapy cuts the risk of these complications.

The other shortcoming, which is linked to the risk of noncompliance, stems from the potential for HIV to develop resistance to drugs. That is happening today. A CDC study found 16% of patients diagnosed with HIV in 10 metropolitan areas from 2007 to 2010 carried antiretroviral-resistant virus. A WHO study found more than 10% of patients starting treatment in six of 11 surveyed countries in Africa, Asia and Latin America had a resistant strain.

Malcolm sees this causing big problems down the line.

It’s a ticking time bomb, he said. It’s just a matter of time before you’re going to get another patient zero who is going to be completely unsusceptible to these inhibitor cocktails and we’re going to be right back to where we were in the ’80s.

Excision plans to head off that scenario by developing EBT101. In parallel, the biotech is working on a clutch of earlier-stage programs, two of which it will move into animal studies using the seed money. Success in those studies would tee Excision up to move candidates against JC virusthe cause of progressive multifocal leukoencephalopathyand herpes simplex virus into the clinic in the next couple of years.

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Artis funds Excision to test whether CRISPR can cure HIV … – FierceBiotech

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Stem Cell Factor Tied to Reduced Risk of Cardiac Events, Death – Anti Aging News

High levels of stem cell factor (SCF) are associated with reduced risk of mortality and cardiovascular events, according to a study published online Aug. 26 in theJournal of Internal Medicine.

(HealthDay News) — High levels of stem cell factor (SCF) are associated with reduced risk of mortality and cardiovascular events, according to a study published online Aug. 26 in theJournal of Internal Medicine.

Harry Bjrkbacka, Ph.D., from Lund University in Sweden, and colleagues examined the correlation between circulating levels of SCF and risk for development of cardiovascular events and death. SCF was analyzed from plasma from 4,742 participants in the Malm Diet and Cancer Study; participants were followed for a mean of 19.2 years.

The researchers found that participants with high baseline levels of SCF had lower cardiovascular and all-cause mortality and reduced risk of heart failure, stroke, and myocardial infarction. There was a correlation for smoking, diabetes, and high alcohol consumption with lower levels of SCF. After adjustment for traditional cardiovascular risk factors, the highest versus the lowest SCF quartile remained independently associated with lower risk of cardiovascular (hazard ratio, 0.59; 95 percent confidence interval, 0.43 to 0.81) and all-cause mortality (hazard ratio, 0.68; 95 percent confidence interval, 0.57 to 0.81) and with lower risk of heart failure (hazard ratio, 0.5; 95 percent confidence interval, 0.31 to 0.8) and stroke (hazard ratio, 0.66; 95 percent confidence interval, 0.47 to 0.92) but not myocardial infarction (hazard ratio, 0.96; 95 percent confidence interval, 0.72 to 1.27).

“The findings provide clinical support for a protective role of SCF in maintaining cardiovascular integrity,” the authors write.

The possibilities that stem cell therapies present in the prevention, regeneration, and treatment of many health conditions seem to be still untouched. If course, stem cell research is still ongoing and no one is complete stem cell expert yet, but maybe thats a good approach to take. I am not so sure I would be comfortable in this modern area of easily accessible information with a physician that still doesnt consider his or her self a student. Whether your doctor is 65 or 38 I hope they are still open to learning, stated Dr. Ronald Klatz, President of the A4M.

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Stem Cell Factor Tied to Reduced Risk of Cardiac Events, Death – Anti Aging News

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Closer Than Ever to a Cure: Annual FA Fundraiser Sept. 22 in Branford –

For 23 years, North Branford’s Caruso-Bode family has been pushing to find a cure for Friedreich’s Ataxia (FA), even as the life-shortening, degenerative neuro-muscular disorder has continued to deepen its toll on the family’s inspiring, courageous siblings, Sam and Alex Bode. On Friday, Sept. 22, family and friends hope the community will continue to support their efforts, by joining in on an annual night of fun, food and fundraising to help find a cure for FA.

This year’s event has the theme”Living a Happy Life” and gets underway at 6 p.m. at Branford’s Owenego Beach and Tennis Club. Tickets are $50 per person, withappetizers, dinner by Outback Steakhouse, acash bar, araffleand “…many unique participants to entertain guests throughout the evening,” according to an event press release. The releasealso shared Alex Bode’s sentiment thatthe community spirit, friendship, kindness and love experienced at the event each year,”…keeps Sam and I optimistic and really feeling supported.”

The siblings were diagnosed with FA as children. Sam Bode was first diagnosed with FA in 1995; followed shortly by the same diagnosis in Alex.Throughthe years and in many ways, Sam, now 31, and Alex, now 27,have done much to help their mother, Mary Caruso, in raising awareness and funding for research as well as workingto promoteacceptance of differences.Caruso was also afounding member of nationalnon-profit Friedreich’s Ataxia Research Alliance (FARA), which was started in September 1998 by a group of FA patient families and three of the world’s leading FA scientists. Proceeds from the Sept. 22 event will help FARA continue to fund research.

In the last 20 years, research has progressed to the point that scientists are nowcloser than ever to the hope of finding a cure, said Caruso.Recent gains in gene therapy research, with clinical trials as the hoped-for nextstep,could bring aboutpositive, targeted results.One area of the work, cardiac gene therapy, will zero in on FA-related heart disease, which recently became an issue facing the Caruso/Bode family. The family is also hopeful about news of another promisingarea of research, which couldrestore eyesight loss due to FA.The Bode siblingsrecently lost their eyesight due to the progressive disease.

“These are the losses that really hit home,” said Caruso. “Both Sam and Alex have recently had to stop riding their hand trikes outside, [the] one activity they both enjoyed so much. To watch them lose the few activities they enjoy is so difficult.”

As always, the siblings are continuing to face FA with “such courage,” said their mom. The devastating, progressiveeffects of the disorderare part of a daily battle usually witnessed by only those closest to the family. Becauseso many in thecommunity may not see the struggle, Caruso wonders if perhaps some may feel as if being asked to help her family find a cure for FA may be asking too much.

“I have found part of the loneliness of it is, when you have a progressive disease without a cure, I think people like to say, ‘Holy Cow — them again?’ You get numb to it,” said Caruso. “Unfortunately, that is our life. For us, it’s an ongoing battle, and you have to always stay ahead of the game, and you have to stay optimistic. We’d love to say we have a treatment, or we have something to try; but we don’t yet. That’s the reality of it. But we have try.”

Join the Caruso/Bode family for an evening of fun, food and fundraising to find a cure for Friedreich’s Ataxia; 6 p.m. – 10p.m.Friday, Sept. 22, Owenego Beach and Tennis Club, 40 Linden Ave. Branford. Tickets, $50 available online hereor by calling (203) 246-8820 or (203) 889-6484. All proceeds assist research supported by FARA, a national, public, 501(c) (3) nonprofit, tax-exempt organization. See more information at

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Closer Than Ever to a Cure: Annual FA Fundraiser Sept. 22 in Branford –

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FDA Vows Modernization to Keep Up With Biotech Advances – Bloomberg


September 7, 2017, 2:04 PM EDT

A week after its landmark approval of the first treatment thatworks by genetically altering a patients cells, the U.S. health regulator vowed to modernize to keep up with the fast-moving field of biotechnology research.

We are at a point in the history of medicine that is similar to other great inflections in science where fundamental principles of science and medicine became firmly established as part of a leap in public health, Food and Drug Administration Commissioner Scott Gottlieb said in a speech in Washington. FDAs goal is to make sure that our policies are as scientifically advanced as the products were being asked to evaluate.

Gottllieb vowed to betteradjust to the complexities of novel therapies and make sure the agencys policies match the challenges faced by companies looking to follow in the footsteps of Novartis AG, whose Kymriah drug was just approved for pediatric patients with a hard-to-treat form of leukemia. The FDA is evaluating more than 550 applications to test gene therapies and 76 related to CAR-T, the same class of compounds as Kymriah, Gottlieb said in his address to Research America, a nonprofit public education and advocacy group dedicated to health and science research.

The speech could be good news for the developers of therapies using the patients own immune system to attack tumors, including Kite Pharma Inc., which is awaiting approval for a CAR-T treatment. FDAs faster-than-expected approval of Novartiss Kymriah sent biotech shares higher last week. That optimism was tempered this week when one drugmaker halted two studies of an experimental blood cancer therapy after a patient died — a reminder of the major risks and safety concerns in the nascent field.

Gottlieb focused his talk on the earliest stage of drug development, before potential new compounds make it into patients. The agency will engage earlier with companies and researchers working in these new areas, including technology platforms like gene therapy, cell therapy and regenerative medicine, he said.

Some academic and industry drug developers arent fully aware of what is is needed to get a new product approved, particularly smaller groups that often are working with the most innovative technology, he said. Others overestimate the amount of information the agency needs to start studies in patients. FDA staff will work with researchers to eliminate unnecessary steps and incorporate new testing approaches that may help cut costs and speed the approval process, he said.

Information that is gleaned from early work in CRISPR, a technology that allows researchers to easily manipulate genes in a way that many hope will one day be used to treat disease, may be used to hasten development of other products, the commissioner said.

Read More: Groundbreaking cancer research — a QuickTake on immunotherapy

In many cases, the main challenges of novel medicines arent clinical questions about how well they work and their immediate safety, but newer issues related to how they are produced and delivered to the patient, the commissioner said. Manufacturing CAR-Ts like Kymriah, for instance, involves extracting infection-fighting cells from the patients blood; sending them to a centralized plant in New Jersey to get re-programmed; and shipping them back to be re-infused into the patient at medical centers.

The new therapies may also carry long-term risks that may not materialize for years — if ever. Attention will be needed on how the therapies hold up during routine use, with risks and benefits that are closely monitored for years, he said.

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FDA Vows Modernization to Keep Up With Biotech Advances – Bloomberg

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Beware of Social Media Celebrity Doctors – Scientific American (blog)

The celebrity doctor phenomenon is not new to Americans. With the release of his first baby-care book in the 1940s, Benjamin Spock became a household name by helping mothers across America feel more confident in their child-rearing skills, long before the age of social media and daytime television. Now, decades later, some of the most prominent players in the game of celebrity doctoring are integrative medicine expert Andrew Weil, cardiothoracic surgeon turned daytime television health guru Mehmet Oz, and televisions go-to-psychologist, Phil McGraw.

All of these men have come under fire in the past, usually due to questions regarding the medical safety and efficacy of their recommendations. But the controversies surrounding them have hardly made a dent in the profitability of their longstanding empires or in the dedication of their fans. Doctors and researchers have been so riled up by the lack of medical evidence for the recommendations handed down by medical television shows that a 2014 study looked specifically at this issue. Not too surprisingly, only 54 percent of the recommendations studied had even one piece of medical evidence to back them up. And less than 1 percent were accompanied by disclosures of potential conflicts of interest.

But now, in the era of social media influencers, celebrity doctoring is no longer exclusively available through the handful of physicians writing books or starring in television shows; it can be found across just about every social media platform. Medical bloggers, doctor instagrammers, and physician twitterati are all reaching out to the American public, and this is a slippery slope to disaster.

What started as a way to improve professional development for physicians and help disseminate credible information for patients has slowly started to devolve into a world of glamour shots, with physicians often exaggerating their credentials at the expense of a gullible social media audience. As a result, social media has created microcosms of celebrity doctoring that have started to expand unchecked and unfettered, usually at the expense of their target audience.

Todays self-promoting physicians have strayed far from the no advertising rule in the original American Medical Association (AMA) Code of Ethics that was in place from 1847 to 1975mainly to prevent the practice of medicine from turning into a practice of solicitation. And while the rule ended to allow hospitals and medical practices to work on public relations efforts for the betterment of healthcare, we have to wonder about the significant potential for harm that stems from often misleading and misrepresentative healthcare information coming from these physician social media accounts.

With 2.5 million Instagram followers, Dr. Mike Varshavski is one of the most popular young physicians on the social media playing field. His account can often be entertaining, albeit misleading: many of his followers likely do not realize that Dr. Mikes experience is very different from the experiences of the average American physician-in-training, based on previous studies looking at resident quality of life. This is fairly harmless, but he also ventures into some dangerous territory, where the line between physician and social media maven begins to blur. Recently, Dr. Mikes Instagram account has been a collection of promotional photo shoots for companies ranging from Charmin to Kenneth Cole to Braun, raising the question of how appropriate is it for a physician to be profiting from Instagram views of posts on the same platform that provides medical commentary? Unfortunately, my requests for comments from Varshavski went unanswered.

Pop-star status for physicians has the potential for harm, simply because of the power wielded by physicians who have such wide access to the American public. Thankfully, in many instances, the Food and Drug Administration has cracked down on misinformation and false claims from such celebrity physicians as Oz and Weil. Ozs claims regarding potentially unsafe arsenic levels in apple juice caused unnecessary hysteria, while Weils claims for his immune boosting supplements came with zero evidence that they could in fact ward off swine flu.

When the practice of clinical medicine begins to be trumped by individual physician brand-building, patient safety and well being can become endangered. And while many of the mega-media physicians often do face scrutiny for their practices, physicians who are merely social media celebrities attract less, even though they might have just as large an audience.

I am not advocating for a witch hunt, but physicians should be held to high clinical standards across every platform in which they practicefrom their clinics to their Instagrams. Unfortunately, clinical standards seem to disappear in the realm of social media, where private practice physicians tout affiliations with academic institutions that they truly have no day-to-day dealings with; pediatric physicians branding themselves as integrative medicine experts for adults; internal medicine physicians branding themselves as skincare experts; and even non-endocrinologists branding themselves as thyroid and adrenal gland experts and pioneering hormone revolutions. The list goes on ad nauseam. Maybe we should have kept some form of the AMAs original no advertising rule around.

Ultimately, there is an almost complete lack of evidence about the long-term effects of social media on the practice of medicine, and right now, there are several accounts that could potentially be deceiving their followers. So what can be done in the meantime? Take everything you see, read, and hear from social media physicians with a grain of salt. Google their credentialsbecause for nearly all physicians with legitimate training, this information is readily available online. Lastly, take some time to scrutinize those credentials to understand if their current area of medical practice is consistent with their training.

It’s wise to remember thatnot everything natural is safe, and not all expert advice is sound.

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Beware of Social Media Celebrity Doctors – Scientific American (blog)

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Depression: The Taboo Topic in Church – Beliefnet

Awhile back, I posted on my Facebook page a question, Is it easy to talk about depression in the church? The overwhelming response to the question was, No. In fact, the church was the last place most people felt they could discuss the subject that affects 1 out of 10 people in our country. We need to do better. We need to understand what depression is all about.

Most people are unaware of the many causes of depression. It is a complicated disorder that requires on-going attention and treatment.

Depression can be a result of medical conditions such as hypothyroidism, Cushings, heart disease, sleep apnea, strokes, Parkinsons, Alzheimers, hormonal imbalances, HIV and AIDS, cancer, autoimmune disorders, seizure disorders and chronic pain.

Depression is also associated with substance abuse and withdrawal from long-term use of many drugs such as cocaine, sedatives, narcotics and steroids.

It is more common in people with a family history of mental illness, suggesting genetic involvement and heritable traits. And people with depression experience biological changes in their brains. Brain chemicals go out of balance and hormone changes can create depressive symptoms.

Traumatic life events such as childhood trauma, death, loss, financial pressures and stress that strains a persons ability to cope all play a role as well.

Certain personality traits make a person more susceptible to depression. Medication side-effects can cause depression. For example, a common medication such as Accutane, used to treat acne, has a side effect of depression in some people.

While the causes of depression are complicated, treatment is available and effective. We know the signs: difficulty concentrating, fatigue, feelings of hopelessness, guilt, worthlessness, helplessness, insomnia or excessive sleeping, loss of pleasure, overeating or appetite changes, sad, anxious or empty feelings, and thoughts of suicide.

If you struggle, dont do so in silence. Tell your physician or a mental health professional and get the help you need. Lets all be a part of making the church aware that people in our congregations struggle in this area and need to discuss depression without the stigma attached or some accusation of having little faith. Based on all the possible ways people can experience depression, dont judge, rather love and encourage people to get help.

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Depression: The Taboo Topic in Church – Beliefnet

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New therapy could protect diabetic bones – Science Magazine

A new therapy changes the balance of osteoblasts (pictured here) and fat cells in the bone marrow, leading to stronger bones.

Science Picture Co/Science Source

By Emma YasinskiSep. 5, 2017 , 2:59 PM

A drug that can reverse diabetes and obesity in mice may have an unexpected benefit: strengthening bones. Experiments with a compound called TNP (2,4,6-trinitrophenol, which is also known as picric acid), which researchers often use to study obesity and diabetes, show that in mice the therapy can promote the formation of new bone. Thats in contrast to many diabetes drugs currently in wide use that leave patients bones weaker. If TNP has similar effects in humans, it may even be able to stimulate bone growth after fractures or prevent bone loss due to aging or disuse.

As more and more patients successfully manage diabetes with drugs that increase their insulin sensitivity, doctors and researchers have observed a serious problem: Thedrugs seem to decrease the activity of cells that produce bone, leaving patients prone to fractures and osteoporosis.

There are millions and millions of people that have osteoporosis [with or without diabetes], and it’s not something we can cure, says Sean Morrison, a stem cell researcher at University of Texas Southwestern in Dallas. We need new agents that promote bone formation.

Morrison and his colleagues have shown that a high-fat diet causes mice to develop bones that contain more fat and less bone. The diet increased the levels of leptina hormone produced by fat cells that usually signals satiety in the brainin the bone marrow, which promoted the development of fat cells instead of bone cells. That suggests that nutrition has a direct effect on the balance of bone and fat in the bone marrow.

After reading Morrisons work, Siddaraju Boregowda, a stem cell researcher at the Scripps Research Institute in Jupiter, Florida, was reminded of genetically altered mice that dont gain body fat or develop diabetes, even when fed high-fat diets. He and his boss, stem cell researcher Donald Phinney, wondered whetherthose mice were also protected from the fattening of the bone marrow that accompanies a high-fat diet.

They contacted Anutosh Chakraborty, a molecular biologist who was studying such mice down the hall at Scripps at the time. The animals lack the gene for an enzyme called inositol hexakisphosphate kinase 1 (IP6K1), which is known to play a role in fat accumulation and insulin sensitivity. The scientists suspected that the lost enzyme might affect the animals’ mesenchymal stem cells (MSCs)stem cells found in the bone marrow that are capable of developing into both thebone cells and fat cells that make up our skeletons. If too many fat cells develop, they take the place of bone cells, weakening the bone.

The researchers fed genetically altered and normal mice a high-fat diet for 8weeks. Not only did the genetically altered mice develop fewer fat cells than their normal counterparts, but their production of bone cells was higher than that of the normal mice, the team reported last month in Stem Cells.

The scientists then set out to see whetherthey could use a drug to achieve the same effect in normal mice. For 8weeks, they fed normal mice a high-fat diet and gave them daily injections of either TNP, a well-known IP6K1 inhibitor, or a placebo. When they analyzed the animals bones and marrow, they found that mice that had received TNP had significantly more bone cells, fewer fat cells, and greater overall bone area. The IP6K1 inhibitor apparently protected the mice from the detrimental effects of the high-fat diet.

The study provided thesurprising result that one new therapy currently being explored to lower insulin resistance promotes, rather than decreases, the formation of bone in mice, says DarwinProckop,a stem cell researcher at Texas A&M College of Medicine in Temple, who was not involved in the work.

The researchers still need to figure out how to deliver TNPs effects only to MSCs, instead of the entire body, given that it sometimes blocks other enzymes along with IP6K1. Inhibition of IP6K1 is a promising target for patients with both diabetes and obesity, Boregowda says. He says he and his colleagues are now enthusiastic about testing their findings in a wide range of bone-related diseases and disorders. It might even help heal broken bones, he speculates.

Phinney, on the other hand, is aiming even higher. He wonders whetherthe therapy could also be useful for space travel, because bones are especially vulnerable to deterioration in zero gravity. Its a whole new field of science and drug discovery.

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New therapy could protect diabetic bones – Science Magazine

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Stem Cell Therapy: A Lethal Cure – Medical News Bulletin

Stem cell therapy is a two-step process. First, the patients blood cells are destroyed by chemotherapy, radiation therapy or immunosuppression. This conditioning process also eradicates any cancer cells that survived first-line treatment. Second, the patient receives stem cells harvested from a donors bone marrow or peripheral blood (circulating blood). While this can be an effective cure, it can cause graft-versus-host disease (GVHD) in up to 50% of patients. GVHD is more likely to develop in patients who have received a peripheral blood transplant and can kill 15%-20% of patients.

Two types of GVHD can develop, acute and chronic, and patients may develop either one, both or neither type. GVHD is less likely to occur and symptoms are milder if the donor cells closely match those of the patient. Acute GVHD can develop within 100 days of a transplant. The first step of stem cell therapy can cause tissue damage, and bacteria from the gut can escape into the bloodstream. This primes the patients antigen-presenting cells (cells that activate the immune response), which subsequently encourage donor T cells to proliferate and attack the patients tissues. Symptoms include vomiting, diarrhea, skin rashes, nausea, vomiting and liver problems. This can be resolved relatively quickly in one third of patients using immunosuppressive treatments, but some patients can progress to chronic GVHD.

The biological mechanisms responsible for chronic GVHD are not completely understood, but scientists believe that other immune system cells from the donor (B cells and macrophages) are stimulated and damage the patients tissues. Symptoms include dry eyes, mouth sores, muscle weakness, fatigue and joint problems.

Unfortunately, development of effective treatments for GVHD is not keeping up with the increasing number of GVHD patients or with advances in understanding this disease. At present, standard treatments include corticosteroids and drugs that reduce IL-2, an immune system chemical that helps T-cells multiply and diversify. These treatments have various side effects including suppressing the patients immune system, thereby increasing risk of infection.

One challenge stalling drug research is that a small degree of graft-versus-host response must occur for successful stem cell therapy: donor cells will destroy any cancer cells that remain after the first stage of therapy. This challenge is discussed in a recent article in Science Health.Although several treatments have been trialed, success is variable and often targets only acute GVHD or chronic GVHD. Biomarkers have also been detected that may help identify individuals at risk of developing severe GVHD, information that may aid the development of personalized treatment strategies. Drugs that have been approved for other diseases, but not for GVHD, show promise and include ibrutinib for chronic GVHD (approved for specific blood cancers) and ruxolitinib for acute GVHD (approved for bone marrow disorders).

The impact of stem cell therapy must not be underestimated: up to 50% of recipients will develop GVHD. Unfortunately, some individuals will develop chronic GVHD, a condition that is just as difficult to survive as cancer. This highlights the importance of developing continued care strategies for individuals receiving stem cell therapy as a final defence against cancer.

Written byNatasha Tetlow, PhD

Reference: Cohen J. A stem cell transplant helped beat back a young doctors cancer. Now, its assaulting his body. Science Health. 2017. Available at: DOI: 10.1126/science.aan7079

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Stem Cell Therapy: A Lethal Cure – Medical News Bulletin

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My son died of cancer: Why I’m celebrating his birthday with stem cell awareness – DailyO

Grief is a personal matter.Each of us has our own mechanisms to copethere is no format set in stone, there are no boundaries. For me, the week leading up to my son Arjan Vir’s birthday has always been the most difficult to deal with.

I am overwhelmed by a well of emotions: On the one hand, there are all those happy memories, so much excitement building up to planning those wonderful birthday parties themes to be decided, lists to be made, cards to be distributed, menus, games and oh, the return gifts one mustn’t forget and then this sudden feeling of hollowness, the sinking depths of which words cannot describe.

Beyond words

I lost my 26-year-old son Arjan Vir to Leukaemia in 2012. Arjan was one of those hugely social people with an enviable optimism about him he loved to have people around him and had the enormous ability to attract people, make friends and share his life with them. His friendships were deeply honest and truly meaningful, there was nothing hollow about them. Those around Arjan loved his happy-go-lucky nature and his laidback attitude towards life.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other. Photo:Simi Singh

My son never lost his ability to make friends despite the battle he was fighting with cancer. Arjan had a battalion of friends in the hospital: ward boys, nurses, lab technicians and resident doctors could be seen about his room whenever they had spare time; some asking for advice on which phone to buy, to have the odd computer issue sorted, if nothing else, just to watch him play computer games.

Losing Arjan did not just leave us his family and friends with an irrevocable sense of vacuum, it was felt by the many lives he had touched in some way or the other.

An intensely sensitive child, Arjan worried more about others than himself he was an avid reader, wrote beautiful poetry and had an imagination that went beyond words.

His passion for computer games had pre-determined his career options, he had decided to study computer graphics and 3D computer animation. Even at the hospital, as he underwent treacherous rounds of chemotherapy, cycle after cycle, his imagination worked overtime planning some game or the other based on his treatment.

Knowing BMT

A Leukaemia patient, Arjan needed a bone marrow transplant (BMT). In a layperson’s terms, BMT means that the unhealthy bone marrow is killed under highly sanitised conditions by giving the patient very high doses of chemotherapy and radiation and replaced by a healthy bone marrow. That sounds perfectly simple, but bone marrow transplant remains a complicated and dangerous procedure.

What consequences does that come with?

For the uninitiated, bone marrow is the soft tissue where all our vital blood components RBCs, WBCs, platelets, plasma and stem cells are formed. Killing one’s bone marrow essentially means there is no immunity left to take care of our body.

Where does the healthy bone marrow come from if we are to attempt to rid the body of cancer?

There are two broad types of BMT: Autologous where the unhealthy bone marrow from our body is removed, worked upon or mutated and replaced, and the allogenic transplant in which another person’s healthy bone marrow replaces our own.

With the second type of transplant come incredible complications and the daunting task of finding the donor bone marrow that must replace ours: one needs to find another person whose DNA is identical to ours. The first and most obvious choice, of course, would be a sibling.

However, the chances of finding the identical DNA HLA typing that matches your siblings’ is only 1:4, and if such a match isn’t possible, where do we go?

In Arjan’s case, our younger son’s HLA typing did not match, and the chances of finding an unrelated donor match were one in a million.

This was the worst possible news we could get, worse than the news of Arjan being diagnosed with Leukaemia.

How does one find an identical HLA typing match in this whole world where do you start, whom do you turn to?

[Photo: Weill Cornell Medecine]

Discovering stem cell registry

In 2012, there were no substantial HLA typing registries in India unlike in developed countries, which maintain nationwide registries that are linked to the worldwide bone marrow registry.

The doctors guided us to approach All India Institute of Medical Sciences (AIIMS) while AIIMS did not have a significant registry of its own, it had a membership with the World Marrow Donors Association (WMDA), and hence could do a worldwide search to find an HLA match for Arjan.

However, institutes likeAIIMS have become desensitised to the urgency that such cases demand and we got no response from them.

At the time, Datri in Chennai was the sole functioning stem cell registry it had about 12,000 donors in its data bank, but we did not get a quick response from them either.

Our son’s doctors here told us that we were sitting on a “time bomb” we needed to act swiftly, we could lose no time and that’s when we decided to take Arjan to the US for his further treatment and then, hopefully, a BMT.

Arjan was distressed to discover the situation in India; when he heard about the lack of registries, his first thought was that once he had recovered, he would set up a meaningful registry at home. His biggest concern was: What do the poor do, where do they go?

And so, five years on, the Arjan Vir Foundation was set up in the memory of our very dear son. Our aim is to run a widespread registry that addresses all blood disorders.

We hope to provide assistance at all stages of treatment, recovery, after care, and the rehabilitation and resettlement of patients.

Registering as a donor is easy: any individual over age 18 can become a donor and be a part of the registry till the age of 60, provided they are healthy.

All that one needs is a simple mouth swab test and the consent to donate stem cells when the need arises. The swabs are sent to a highly-specialised laboratory in the US for HLA typing and the results shared with the worldwide registry maintained by WMDA.

Upon finding a match for a patient, the registry contacts the concerned donor.

The process is not complicated, it is exactly like platelet donation, only a few hours longer: avolunteer must undergo a complete medical check-up prior to donating stem cells and is put on stem cell boosting therapy for about four days before the procedure. No incision is involved and the donor does not require hospitalisation.

It just takes one day of your life and busy schedule to save a life.


Today, as I sat down to write this article, I also planned another kind of a celebration for Arjan’s birthday on September 6: this year, we are holding a camp to bring about awareness about stem cells and register donors at a university in Noida.

Once again there is excitement, albeit of a different kind one held together with a sense of pathos.

Also read: Memories of my mother that Alzheimer’s can’t wipe clean

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My son died of cancer: Why I’m celebrating his birthday with stem cell awareness – DailyO

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Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

On Saturday morning, a convoy of vintage Ford Broncos carrying some very precious cargo made a stop at La Caadas Descanso Gardens.

En route from Childrens Hospital Los Angeles, the motorcade was led by a golden 1971 Bronco with Thousand Oaks resident Tyler Kelly at the helm. Tucked safely into a car seat in the back was 2-year-old Pierce Kelly, known by family and friends as Fierce Pierce, still recovering from a July 21 bone marrow transplant.

At the La Caada home of relatives Donna and Dave McLaughlin, Pierce will recuperate under the watchful eye of mom Aubrey. For 100 days following the procedure, he must reside within a 30-minute drive of Childrens Hospital for monitoring.

Saturdays 13-mile drive was just one portion of a tumultuous journey the Kellys have been on since April 7, when Pierce was diagnosed with acute myeloid leukemia. His chance of surviving the devastating illness with treatment alone was only 50%, according to mom Aubrey. But there was one hope if the Kellys could find a bone marrow donor, Pierces odds would improve by at least another 15%.

We were at the mercy of whoever had registered, Aubrey Kelly recalled.

Among the nearly 13.5 million Americans already listed as donors on the Be the Match Marrow Registry, there were no donors close enough to be a match with Pierce.

Raquel Edpao, a community outreach specialist for Be the Match, said on any given day there are 14,000 people like the Kellys, searching registries for a bone marrow match. Its her job to help educate people how simple it is to join the registry and to donate if called.

Potential donors register online at, then receive and turn in a cheek swab. After that, theyre contacted if they are a potential match for someone. Edpao estimates about one out of every 430 registrants will be asked to donate.

There are so many misconceptions about donating, she said, invoking myths about spinal drilling, painful extractions and missed days at work. Its usually as simple as donating blood.

In about 20% of cases donors are asked to undergo a marrow extraction, a 45-minute outpatient procedure involving a general anesthetic.

Luckily for the Kellys, a search of donors worldwide returned a single donor in France whose human leukocyte antigen (HLA) protein was a 10-out-of-10 match with Pierces. While the marrow was shipped, the 2-year-old underwent chemotherapy to destroy most of his damaged stem cells in preparation for the donation.

Its a fine balance of leaving him with enough cells to receive the new ones, but not so many that the new cells dont have enough room to grow, Aubrey Kelly said, explaining how her sons blood type switched from A positive, his own type, to the donors O negative.

Pierces recovery from the transplant requires a sterile environment that means he cannot stay with siblings Sierra, 4, and 6-month-old Harper. Donna McLaughlin, a cousin of Aubrey Kellys dad, said she and husband Dave were happy to offer their home in La Caadas Paradise Valley neighborhood for his recovery.

Ive worked for the past week cleaning my house its never been so clean, she said of her preparation for Pierce and Aubreys 57-day visit. Im being paranoid, I know, but he is going to be OK on my watch.

Knowing he would have to return to Thousand Oaks to take care of Pierces sisters, Tyler Kelly wanted to ensure his sons trip from the hospital would be a special one. The Bronco the same vehicle his mother drove to the hospital in 1981 so he could be delivered, and the same one he and Aubrey have used to get to the delivery room in time for the birth of their own three children seemed a fitting conveyance.

We wanted to continue the tradition, he said.

Hoping to assemble a retinue for the drive, Tyler Kelly reached out to enthusiast club SoCal Broncos and Several people responded, including Agoura Hills Bronco owner Dan Bennett, for whom the cause was personal. About 10 years ago he saved a life by donating his own bone marrow.

To be able to go in and help play an intrinsic role in saving someones life is a really special thing, Bennett said. I think everybody should do it.

Twitter: @SaraCardine

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Convoy from Children’s Hospital to La Caada carries precious cargo a 2-year-old bone marrow recipient – Los Angeles Times

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Appeal to help firefighter battling cancer caused by clinical trial for Crohn’s disease – Deadline News

A VETERAN firefighter is battling blood cancer caused by taking part in a trial of a new treatment for his Crohns disease.Gary Dall, who has spent almost 30 years saving lives, has an aggressive form of myelodysplasia (MDS) a type of cancer where the bone marrow fails to make enough healthy blood cells.The 49-year-old from Kirkcaldy, Fife, agreed to take part in a clinical trial to cure his Crohns disease seven years ago.Gary says he was advised there was a low risk of developing cancer as a result of the treatment, which involved a transplant of his own stem cells, taking medication and undergoing chemotherapy.Last year, doctors discovered the father-of-fours blood count was low and bone marrow tests showed that he had MDS.The only cure for Gary is for him is to have a second stem cell transplant which he can only have when he finds a suitable donor.Now, the Scottish Fire and Rescue Service and blood cancer charity, The Anthony Nolen Trust are holding a public donor event at Kirkcaldy fire station next weekend to find a donor.Gary, a group manager at Kirkcaldy station, was on medication for Crohns, a long-term condition which causes inflammation of the digestive system and currently affects 115,000 people in the UK.Seven years ago, his medication for the disease stopped working.

Gary said today (thu): I was offered a clinical trial and took it. The trial involved taking medication to increase my blood cells and then chemotherapy.They would have told me about the risks involved but with the state I was in, I cant remember much.The risks for something like this are low.Speaking about the appeal for a second stem cell donor he added: Ive been told theres a 60% chance I will find a match because Im white and British so match a lot of people on the register but the more people that donate, the more will help save others lives too.Gary told his local paper this week: It was just one of those things that a treatment for one disease led to me getting another. Its not nice, but Im just taking things as they come and hoping that a match can be found.When we first found out my family were shocked, and it has taken a bit of getting used to.After hearing that fan Gary was in need of a transplant, members from Raith Rovers Football team signed up to a national bone marrow register.Kirkcaldy fire station will be holding a drive on September 16 to encourage members of the public to join a register to potentially become a bone marrow donor.Healthy people, aged between 16 and 30 are eligible to register to become stem cell donors.They will have to fill out a form and provide a saliva sample on the day but are advised not to eat or drink anything half an hour before attending.There is currently no cure for Crohns disease but medics provide treatment to stop the inflammatory process, relieve symptoms and avoid surgery wherever possible.Past research has shown that patients with Crohns disease of the small and/or large intestine have an increased risk of developing cancer at these areas.Gary, who was diagnosed with Crohns disease 13 years ago, today revealed that the treatment puts 95% of patients into remission. Tragically, he has been left with bith Crohns and cancer.He said the trial was offered via NHS Fife. Called Autologous Stem cell Transplantation International Crohns (ASTIC), the treatment has been undergone by crohns sufferers worldwide.

Today Gary said: The medication I was given wasnt working at all so I was told about about the ASTIC trial instead of having to get my bowels removed.It was an attempt to cure it. 95% of people over the world that have had it go into remission. Unfortunately I was one of the five percent that didnt.Gary said his blood cancer is only curable if he gets a matching donor.He added: The drive isnt just about me though, its about everyone else who could be saved by people getting registered as donors.Treatment would involve destroying Garys own bone marrow cells with chemotherapy before having stem cells from a donor fed into his bloodstream via a drip.Amy Bartlett, Register Development Manager for Scotland at the Anthony Nolan Trust, said: We were deeply saddened to learn about Garys diagnosis, and we will support him in every step of his search for a lifesaving donor.Im looking forward to working with our close partners in the SFRS in Kirkcaldy to recruit even more potential lifesavers to the Anthony Nolan register every person who signs up has the potential to help someone like Gary whos in need of a stem cell transplant.We know from the amazing response to Ava Starks appeal for a lifesaving donor how brilliant the people of Fife, and Scotland, are in rallying behind someone in desperate need.

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Appeal to help firefighter battling cancer caused by clinical trial for Crohn’s disease – Deadline News

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South Bend man a ‘walking miracle’ after cancer treatment breakthrough – South Bend Tribune

Scott McIntyre calls himself a walking miracle, and he wants to tell the world about it.

I was given three to six months to survive and Im 16 months in remission, said the 53-year-old South Bend man. I would love to get the story out and let people have hope. Dont give up. You never know.

On Friday, a University of Chicago Medicine marketing team shot video and still images of Scott at Shamrock Truck Sales, the semi-truck sales and service business he co-owns near LaPaz. His face will adorn billboards, digital and print ads in Chicagoland and northwest Indiana as soon as the U.S. Food and Drug Administration approves what UCM is calling a revolutionary breakthrough in cancer treatment.

If that FDA approval comes and UCM is preparing for it to come very soon UCM will have one of the only facilities in the Midwest certified to administer chimeric antigen receptor T-cell infusion, or CAR T-cell, a newer form of immunotherapy.

Video: CAR T treatment gives hope in cancer fight

In CAR T-cell therapy, a type of white blood cell called T-cells are extracted from the patients blood and modified in the lab to recognize specific cancer cells. These supercharged T-cells are then infused back into the patient, where they search out and destroy cancer cells.

The therapy, often described as a living drug because it is customized with each patients T-cells, will be marketed as Kymriah by Swiss pharmaceutical maker Novartis.

Scott was excited to hear news Wednesday that the FDA approved the same treatment for a form of childhood leukemia, meaning, he hopes, that it won’t be long before it’s approved for his form of cancer, diffuse large B-cell lymphoma. The FDA called the approval “historic” because it marks the first cell-based gene therapy approved in the United States.

Scott is one of 130 patients nationally in the clinical trial for his form of lymphoma, and he was the first to receive the treatment at UCM. That happened in May 2016, when he had exhausted all other options.

Scott has been feeling good for just less than a year. Chemotherapy has taken his hair three times but he has a full head of it once again. He can play an entire round of golf with his son. An avid Notre Dame football fan and season ticket holder, he had to miss each game in 2015, but plans to attend every game this season.

In May 2013, Scott noticed a painful growth in his groin area. His family doctor, Dr. Joseph Caruso, said he had developed a swollen lymph node, which could have resulted from his body trying to fight off an infection. Caruso asked him if he had recently had an infection, and Scott recounted recently stepping on a rusty nail while the roof on his home was being replaced. Caruso prescribed an antibiotic and the swelling seemed to go away.

But four months later, while in the shower, Scott noticed another lump under his arm. He went back to Caruso, who referred him to South Bend-based Beacon Health System oncologist Dr. Thomas Reid. After some scans, Reid diagnosed Stage 3 lymphoma.

Reid administered the standard treatment, four cycles of a chemotherapy regimen known as R-CHOP, an effective but highly toxic blend of drugs causing severe side effects. The fourth cycle had to be delayed because he developed appendicitis, and it was tougher than the first three.

After all of that, the cancer started growing again just two months later.

Reid referred him to Dr. Sonali Smith, professor of medicine and director of UCMs lymphoma program. Smith and her team knew the CAR T-cell therapy was being investigated in a few select centers. Their short-term goal was to keep him alive until they could be cleared to administer the clinical trial.

In February 2015, Scott received a stem-cell transplant, which went smoothly. But three months later, the cancer again started growing. Participation in two more clinical trials and some precisely targeted radiation therapy bought a little more time, but by late 2015, his lymphoma was gaining on him.

Then, in early February 2016, the UCM team received the go-ahead for the CAR T-cell treatment and began harvesting his T cells, a process that resembles dialysis. Scott said another patient had been slated to receive the treatment first, but that patient died.

It was during an appointment in May 2016, just a week before the treatment, that Scott first grasped how close he was to dying. Smith told him the treatment could cause severe side effects, including death. Five people in the trial had died.

I said, I understand. What other options do I have? Scott recalled. She says, Oh youve already surpassed all expectations. I said, What do you mean by that? And thats when she said, after the stem cell, if it comes back, life expectancy is six months. It was a rough day. On the way home I was pretty shaken up.

A little after 9:30 a.m. on May 18, 2016, Scott, sporting a Notre Dame baseball cap, was prepared for the treatment. Carefully observing was Dr. Michael Bishop, professor of medicine and director of the Hematopoietic Cellular Therapy Program at UCM, and about a dozen members of his team. A technician brought in his modified T-cells, thawed them out and infused them into Scott intravenously.

Ten minutes later, the treatment was finished. Afterward, he and his wife Cindy spent 28 days in the hospital and then were required to live in an apartment within 10 minutes of the university hospital. They were allowed to move back home to South Bend in July, about two months after the treatment.

Its incredible, Cindy said of Scotts recovery thus far. We did not realize what we were getting into, all of the risks, until days before. She (Dr. Smith) may have mentioned it but it didnt sink in. We both realized that win, lose or draw, theyre going to learn so much, just from how he responds to it.

Cindy praised how well Drs. Reid and Smith worked together between South Bend and Chicago, and how they told them just enough to be informed without telling them so much that they panicked.

She said, theres this trial, Cindy said. This is for you. You were designed for this trial and it was designed for you. We just have to keep you going until we can give it to you.

The treatment was on a Wednesday. By Friday night, his first fever came and it wasnt a surprise. Once they enter the body, each T cell multiplies rapidly, producing thousands of offspring. Then they launch a vigorous assault. All of that warfare occurring inside the body can cause severe flu-like symptoms: fever, swelling, low blood pressure.

On Sunday his fever spiked to 104 degrees. They packed him in ice around his neck and under his arms, and managed to break the fever without sending him into intensive care.

He also experienced some neurological effects, including tremors, cognitive delays and blurred vision.

Now, more than a year later, Smith still wants to see Scott every three months, and he remains very susceptible to infections because his immunity will always be compromised not from the CAR T-cell but from all of the chemotherapy. He still has some swelling because the scar tissue from three surgeries restricts the flow of lymphotic fluids.

I feel it all the time and I have very limited range of movements but it doesnt stop me, he said.

Unless the lawn needs to be mowed, then it really bothers him, she said. Some things will never change.

She said she never imagined she had married a pioneer.

I knew I had married somebody very unique, very special, but definitely not a pioneer, she said. He was the last person you ever thought would be sick. Doesnt drink. Doesnt smoke. Never had ventured on the wild side. This wasnt supposed to happen.

So far the FDA has only approved T-cell treatments for blood cancers, such as lymphoma and leukemia, but not solid tumor cancers, such as breast and colon cancer, which kill many more people. But Bishop of UCM said that day is coming. He expects those clinical trials to begin within a year or two, and receive FDA approval within about five years.

Its very exciting, Bishop said. The technology is a little more complicated but it has the potential to treat a broad spectrum of cancers. Ive been doing this for 25 years and this is one of the most significant advances Ive seen in my career.

Meanwhile, Scott will keep telling his story of hope to everyone he can, including himself. Bishop said Scott’s cancer has a 10- to 20-percent chance to recur.

Youre still thinking that the other shoe can drop, Scott said. The mantra I use when negative thoughts enter my head is, Alright Scott, are you giving up? No. Are you quitting? No. Then shut up. I dont know if that will ever go away.

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South Bend man a ‘walking miracle’ after cancer treatment breakthrough – South Bend Tribune

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