Page 4«..3456..1020..»

Archive for the ‘Gene Therapy Research’ Category

Gene Therapy | Pfizer: One of the world’s premier …

Gene therapy is a technology aimed at correcting or fixing a gene that may be defective. This exciting and potentially transformative area of research is focused on the development of potential treatments for monogenic diseases, or diseases that are caused by a defect in one gene.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

The technology involves the introduction of genetic material (DNA or RNA) into the body, often through delivering a corrected copy of a gene to a patients cells to compensate for a defective one, using a viral vector.

Viral vectors can be developed using adeno-associated virus (AAV), a naturally occurring virus which has been adapted for gene therapy use. Its ability to deliver genetic material to a wide range of tissues makes AAV vectors useful for transferring therapeutic genes into target cells. Gene therapy research holds tremendous promise in leading to the possible development of highly-specialized, potentially one-time delivery treatments for patients suffering from rare, monogenic diseases.

Gene therapy research holdstremendous promise

Pfizer aims to build an industry-leading gene therapy platform with a strategy focused on establishing a transformational portfolio through in-house capabilities, and enhancing those capabilities through strategic collaborations, as well as potential licensing and M&A activities.

We're working to access the most effective vector designs available to build a robust clinical stage portfolio, and employing a scalable manufacturing approach, proprietary cell lines and sophisticated analytics to support clinical development.

In addition, we're collaborating with some of the foremost experts in this field, through collaborations with Spark Therapeutics, Inc., on a potentially transformative gene therapy treatment for hemophilia B, which received Breakthrough Therapy designation from the US Food and Drug Administration, and 4D Molecular Therapeutics to discover and develop targeted next-generation AAV vectors for cardiac disease.

Gene therapy holds the promise of bringing true disease modification for patients suffering from devastating diseases, a promise were working to seeing become a reality in the years to come.

Continue reading here:
Gene Therapy | Pfizer: One of the world's premier ...

Pfizer commits $100M for a gene therapies plant in North Carolina – FiercePharma

Pfizer committed to building a $100 million gene therapies plant in North Carolinaand in exchange, North Carolina committed to providing the drugmaker with a quarter-million dollars' worth of help.

Pfizer will expand an 11,000-square-foot plant in Sanford, North Carolina that it acquiredlast year when it bought gene therapies biotech Bamboo Therapeutics in a deal valued at up to $688 million.Bamboo bought the facilitylast year from the University of North Carolina about the time that Pfizer made is initial investment in the company.

The drugmaker considered building a facility in Massachusetts where it has other research and manufacturing operations but decided on North Carolinawhere it will receive a $250,000 performance grant from the state for the project and its 40 jobs.

RELATED:Pfizer looks at building major gene therapy manufacturing facility in North Carolina

Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy, Lynn Bottone, site leader at Pfizer Sanford said in a statement. We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility.

A Pfizer spokeswoman said in an email Tuesday that it was too early in the process to provide any details about the size of the expansion or when it might be producing materials.

Bamboo has already produced phase I and II materials in the facility using what Pfizer said was superior suspension, cell-based production platform that increases scalability, efficiency and purity.

Bamboo is working on gene therapies for certain rare diseases related to neuromuscular conditions and the central nervous system. With gene therapies, genetic material is introduced into a patients body to replacemutations that cause diseaseand the expectation is that treatments may cure the condition.

RELATED: Pfizer doubles down on gene therapy pipeline with $70M Sangamo buy-in

Pfizer is among a number of companies exploring the new area and added to its portfolio this spring when it struck a licensing deal with Richmond, California-based Sangamo Therapeutics, which is working on gene therapies for treating hemophilia A. Under the deal, Sangamo got $70 million upfront and could gain $475 million in biobucks and sales royalties on any medications from the collaboration that gain approval.

Others are building manufacturing facilities as well. California-based BioMarin, recently completed the renovation of a 25,000-square-foot building in Novato, Novato, California, for manufacturing the gene therapies for hemophilia A which its has in clinical trials, the Marin Independent Journal reported Monday.

See the original post here:
Pfizer commits $100M for a gene therapies plant in North Carolina - FiercePharma

Grant enables study of mosquito virus as a genetic lab tool, malaria biocontrol – Penn State News

UNIVERSITY PARK, Pa. A virus that infects a species of malaria-transmitting mosquito could help scientists gain a better understanding of mosquito biology and eventually could lead to methods for stopping or slowing the spread of the disease, according to a researcher in Penn State's College of Agricultural Sciences.

Jason Rasgon, professor of entomology, has received a grant of $1.9 million from the National Institutes of Health to study the virus, called AgDNV. The goal of the five-year project is to develop a toolset that would enable researchers to genetically modify mosquitoes more easily, with an eye toward examining the influence of specific genes on mosquito phenotypes and developing malaria-control strategies.

"This project involves Anopheles gambiae, the main mosquito vector of malaria in Africa," Rasgon said. "Routine genetic manipulation of this species has proven challenging, so the development of novel tools for genetic modification is critical for both applied strategies for malaria control and for basic research into this mosquito's genetics and host-pathogen interactions."

To prove the feasibility of this concept, the research team will insert specific genes into a densonucleosis virus known as a "densovirus" which will infect the mosquito's tissues and express those genes.

"This virus is distantly related to the virus used in human gene therapy," Rasgon said. "So it's almost like gene therapy in the mosquito."

He explained that the densovirus is a tiny virus it contains only three genes and about 4,100 nucleotides and its entire genome can be synthesized artificially and placed into a plasmid, which is a circular piece of DNA.

"Once in that form, we easily can manipulate it and transfect it into insect cells in a dish, where it will make live, infectious virus that will have whatever genetic modifications we've put into it," said Rasgon.

Researchers then can infect mosquitoes either by putting the virus into water with mosquito larvae or by injecting it into adult mosquitoes. The virus then will infect them, and whatever gene was inserted will be expressed.

An Anopheles gambiae mosquito infected with AgDNV (virus) expressing green fluorescent protein.

Rasgon said this system would have great value as a laboratory tool: "If you want to test a gene by turning it on or off, you wouldn't need to develop a transgenic mosquito. You just could pop it into the virus, and it will express that gene in the mosquito for you."

It also could become a biocontrol agent, he said. "You could insert genes that would make the mosquito unable to transmit the malaria parasite or that would kill the mosquito or shorten its lifespan."

This specific virus occurs naturally and would be very safe as a control agent, Rasgon noted. The virus is not a human pathogen and is host-specific, meaning it infects only Anopheles gambiae and not other mosquitoes or nontarget organisms such as vertebrates.

In addition, once infected by the modified virus, adult female mosquitoes can transmit it to larvae by inoculating it into the water when laying eggs. Rasgon's lab also has found that male adult mosquitoes can transmit the virus to females during mating.

Rasgon maintains that this line of research illustrates the unpredictability and serendipity of science he discovered the existence of the virus by accident about 10 years ago.

"We were looking for a particular bacterium in a mosquito cell line using PCR [polymerase chain reaction], and we got a weird band where there shouldn't have been one," he said. "We wanted to know what it was so we sequenced it, and it turned out to be this virus.

"We've been unsuccessfully seeking funding to study it further for 10 years. So receiving this grant also is a testament to the value of persistence in science," he said.

Excerpt from:
Grant enables study of mosquito virus as a genetic lab tool, malaria biocontrol - Penn State News

Skewing the Aim of Targeted Cancer Therapies – Research Horizons

[Note to researchers: mRNA-protein level disparities found in metastatic ovarian cancer in more than 60% of measurements across 4,436 genes; evidence of micro RNA regulation]

Headlines, of late, have touted the successes of targeted gene-based cancer therapies, such as immunotherapies, but, unfortunately, alsotheir failures.

Broad inadequacies in a widespread biological concept that affects cancer research could be significantly deflecting the aim of such targeted drugs,according to a new study. A team exploring genetic mechanisms in cancer at the Georgia Institute of Technology has found evidence that a prevailing concept about how cells produce protein molecules, particularly when applied to cancer, could be erroneous as much as two-thirds of the time.

Prior studies by other researchers have also critiqued this concept about the pathway leading from genetic code to proteins, but this new study,led by cancer researcher John McDonald, has employed rare analytical technology to explore it in unparalleled detail. The study also turned up novel evidence for regulating mechanisms that could account for the prevailing concepts apparent shortcomings.

The concept stems from common knowledge about the assembly line inside cells that produces protein molecules. It starts with code in DNA, which is transcribed to messenger RNA, then translated into protein molecules, the cells building blocks.

That model seems to have left the impression that cellular protein production works analogously to an old-style factory production line: That the amount of a messenger RNA encoded by DNA on the front end translates directly into the amount of a corresponding protein produced on the back end. That idea is at the core of how gene-based cancer drug developers choose their targets.

To put that assumed congruence between RNA production and protein production to the test, the researchers examined -- in ovarian cancer cells donated by a patient -- 4,436 genes, their subsequently transcribed messenger RNA, and the resulting proteins. The assumption, that proverbial factory orders passed down the DNA-RNA line determine in a straightforward manner the amount of a protein being produced, proved incorrect 62 percent of the time.

The messenger RNA-protein connection is important because proteins are usually the targets ofgene-based cancer therapies, McDonald said. And drug developers typically measure messenger RNA levels thinking they will tell them what the proteins levels are. But the significant variations in ratios of messenger RNA to protein that the researchers found make the common method of targeting proteins via RNA seem much less than optimal.

McDonald,Mengnan Zhangand Ronghu Wu published their resultson August 15, 2017 in the journalScientific Reports. The work was funded by the Ovarian Cancer Institute, The Deborah Nash Endowment, Atlantas Northside Hospital and the National Science Foundation. The spectrophotometric technology needed to closely identify a high number of proteins is rare and costly but isavailable in Wus lab at Georgia Tech.

Whereas many studies look at normal tissue versus cancerous tissue, this new study focused on cancer progression, ormetastasis, which is what usually makes cancer deadly. The researchers looked at primary tumor tissue and also metastatic tissue.

The idea that any change in RNA level in cancerous development flows all the way up to the protein level could be leading to drug targeting errors, saidMcDonald, who heads Georgia Techs Integrated Cancer Research Center. Drug developers often look for oddly high messenger RNA levels in a cancer then go after what they believe must be the resulting oddly high levels of a corresponding protein.

Taking messenger RNA as a protein level indicator could actually work some of the time. In the McDonald teams latest experiment, in 38 percent of the cases, the rise of RNA levels in cancerous cells did indeed reflect a comparable rise of protein levels. But in the rest of cases, they did not.

So, there are going to be many instances where if youre predicting what to give therapeutically to a patient based on RNA, your prescription could easily be incorrect, McDonald said. Drug developers could be aiming at targets that arent there and also not shooting for targets that are there.

The analogy of a factory producing building materials can help illustrate what goes wrong in a cancerous cell, and also help describe the studys new insights into protein production. To complete the metaphor: The materials produced are used in the construction of the factorys own building, that is, the cells own structures.

In cancer cells, a mutation makes protein production go awry usually not by deforming proteins but by overproducing them. A lot of mutations in cancer are mutations in production levels. The proteins are being overexpressed, said McDonald, who is also aprofessor in Georgia Techs School of Biological Sciences.

A bad factory order can lead to the production of too much of a good material and then force it into the structures of the cell, distorting it. The question is: Where in the production line do bad factory orders appear?

According to the new study, the answer is less straightforward than previously thought.

The orders dont all appear on the front end of the assembly line with DNA over-transcribing messenger RNA. Additionally, some mutations that do over-transcribe messenger RNA on the front end are tamped down or canceled by regulating mechanisms further down the line, and may never end up boosting protein levels on the back end.

Regulating mechanisms also appear to be making other messenger RNA, transcribed in normal amounts, unexpectedly crank out inordinate levels of proteins.

At the heart of those regulating systems, another RNA called micro RNA may be micromanaging how much, or little, of a protein is actually produced in the end.

We have evidence that micro RNAs may be responsible for the non-correlation between the proteins and the RNA, and thats completely novel, McDonald said. Its an emerging area of research.

Micro RNA, ormiRNA, is an extremely short strand of RNA.

McDonald would like to see tissues from more cancer patients undergo similar testing. Right now, with just one patient, the data is limited, but I also really think it shows that the phenomenon is real, McDonald said.

Many past studies have looked at one particular protein and a particular gene, or a particular handful. We looked at more than 4,000, McDonald said. What that brings up is that the phenomenon is probably not isolated but instead genome-wide.

The studys authors would also like to see rarely accessible, advanced protein detecting technology become more widely available to biomolecular researchers, especially in the field of cancer drug development. Targeted gene therapy is a good idea, but you need the full knowledge of whether its affecting the protein level, McDonald said.

He pointed out that no one is at fault for the possible incompleteness of commonly held concepts about protein production.

As science progresses, it naturally illuminates new details, and formerly useful ideas need updating. With the existence of new technologies, it may be time to flesh out this particular concept for the sake of cancer research progress.

Also READ: Punching Cancer With RNA Knuckles with John McDonald

The research was supported by grants from the Ovarian Cancer Institute, The Deborah Nash Endowment Fund, Northside Hospital (Atlanta), and the National Science Foundation (CHE-452 1454501). Cancer tissues from ovary and omental sites were collected from a cancer patient at Northside Hospital with informed consent under Georgia Institute of Technology Institutional Review Board protocols (H14337). Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of those agencies.

Read more:
Skewing the Aim of Targeted Cancer Therapies - Research Horizons

Gene Editing System Revamped to Target RNA Aggregates Found in Inherited ALS – ALS News Today

Researchers have found a way to break down aggregated RNA molecules that cause diseases such as certain inherited forms of amyotrophic lateral sclerosis (ALS).

As the technique has the potential to treat several diseases which currently lack treatment options, the research team from theUniversity of California, San Diego (UCSD) made sure to engineer the new system so that it could be delivered to specific tissues with non-infectious viruses.

The method builds on a well-known gene-editing system, called CRISPRCas9, but was adapted to target RNA instead of DNA. The new method is called RNA-targeting Cas9, or simply, RCas9.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, the studys senior author, Gene Yeo, said in a press release. He is aprofessor of cellular and molecular medicine at UCSD School of Medicine.

The study, Elimination of Toxic Microsatellite Repeat Expansion RNA by RNA-Targeting Cas9, published in the journal Cell, described how the team rebuilt the Cas9 system to find and chop up disease-causing RNA molecules.

In gene editing, the CRISPRCas 9 system uses an RNA probe that matches a specific stretch of DNA. Once bound to the right gene, the Cas9 enzyme cuts the DNA, which then can be inactivated or edited. The new system targets RNA, and chops it upinstead of editing it.

RNA, whichis largely composed of similar building blocks as DNA, has numerous roles in a cell. For instance, it is used to take a copy of a gene to provide instructions for the cells protein-making machinery.

At times, however, RNA molecules start accumulating what researchers call microsatellite repeat expansions. These are stretches of repeat RNA letters that disrupt the normal activity of the RNA. When found in messenger RNAs, they prevent necessary proteins from being made.

Anabnormal sequence also makes the RNA accumulate in cells, disrupting other cell operations. This can be seen in ALS that runs in families, andin diseases such as myotonic dystrophy and Huntingtons.

In ALS, such repeats are found in the C9orf72 gene, and cause about a third of familial ALS cases, or those that run in families,according to the ALS Association.

Testing the new tool in lab-grown cells derived from ALS patients with such mutations, the team showed that RCas9 could eliminate at least 95 percent of accumulated RNA, seen as dense clusters, or foci, in the cells.

They also discovered that using RCas9 freed proteins that normally bind to RNA in cells. When abnormal RNA starts accumulating in a cell, these proteins get tied up interacting with the aggregates, instead of binding to their natural targets. Researchers said that treated patient-derived cells eventually resembled healthy cells.

For the system to be useful as a human therapy, it needs to fit into a virus the most common way to deliver gene therapy. Normal Cas9 is too large to fit into thevirus typically used. The team solved the issue by removing parts of the Cas9 enzyme required for cutting DNA, making the enzyme small enough to fit.

Yet, many more questions need to be answered before the method can be tried in patients.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, Yeo said. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities and evaluate long-term exposure.

The group has launched a company, Locana, that will work onpreclinical-trial development of the method with the aim of bringing it to patients.

We are really excited about this work because we not only defined a new potential therapeutic mechanism for CRISPR-Cas9, we demonstrated how it could be used to treat an entire class of conditions for which there are no successful treatment options, said David Nelles, PhD, one of two lead studyauthors.

There are more than 20 genetic diseases caused by microsatellite expansions in different places in the genome. Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength, added Ranjan Batra, PhD, the studys other lead author.

Original post:
Gene Editing System Revamped to Target RNA Aggregates Found in Inherited ALS - ALS News Today

Pfizer Plans Gene Therapy Manufacturing Investment in North … – BioPharm International

Pfizer is moving forward with plans to invest in a new clinical and commercial gene therapy manufacturing facility in Sanford, NC, but the work is still in the preliminary stages, said the company. A $100-million investment in the Sanford facilities is expected to create 40 jobs, according to a press release from the North Carolina governors office.

The facility will build upon a technology first developed at the University of North Carolina at Chapel Hill. Gene therapy focuses on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Gene therapy is an important area of focus for Pfizer. In 2016, the company acquired Bamboo Therapeutics, a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research, according to the press release.

A performance-based grant of $250,000 from the One North Carolina (NC) Fund will help facilitate Pfizers expansion. The One NC grant will formally be awarded to Wyeth Holdings, a wholly owned subsidiary of Pfizer. The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

Source: Pfizer, NC Governors Office

Read more:
Pfizer Plans Gene Therapy Manufacturing Investment in North ... - BioPharm International

Americans want a say in human genome editing, survey shows – Los Angeles Times

When it comes to CRISPR, our society has some important decisions to make.

Just last week, scientists reported a new first in the journal Nature: They edited heritable cells in human embryos to treat an inherited form of heart disease. The day after the research was published, a group of genetics experts published a statement calling for further debate before applications of the technology are taken any further in humans.

According to a new survey of 1,600 adults published in the journal Science today, much of the American public shares this desire for engagement in decision-making. Led by Dietram Scheufele, a professor of science communication at the University of Wisconsin - Madison, the study found that while support for gene editing applications varies, a majority of respondents think the public should be consulted before genome editing is used in humans.

Gene editing presents the potential for remarkable benefits.

The potential to cure genetic disease and to ensure the safety of the world's food supply in the face of climate change are perhaps the most exciting opportunities, said Jennifer Doudna, a chemist at UC Berkeley who was an early pioneer of the powerful gene-editing technique CRISPR-Cas9 and was not involved in the new study.

But it also raises some serious ethical questions, especially when we turn our attention to tweaking the human genome, Scheufele said. Many people find some applications like disease treatment valuable, and others like making your children more intelligent morally shaky.

For example, scientists may eventually develop a cure for what some people dont consider an illness like a disability, Scheufele said. Would those who chose not to undergo genetic therapy or who couldnt afford it then be discriminated against even more as a result?

These and other ethical concerns go beyond the bounds of science, Scheufele says, and his poll results show that the public wants to be involved in the debate.

Oregon Health & Science University

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease.

Embryos develop into blastocysts after co-injection, which could someday be used in fertility clinics to help people trying to have children free of genetic disease. (Oregon Health & Science University)

Because of the fast-moving progress of gene editing research and the vast potential for both beneficial applications and negative consequences, many experts have called for public engagement on the issue including in a consensus report released this year by the National Academy of Sciences (NAS) and the National Academy of Medicine (NAM).

The new study strove to answer some questions emerging from the National Academies report. First, how do people feel about different applications of gene editing? And secondly, do Americans agree that the public should be consulted on gene editing applications? Similar questions had been asked in previous polls, but the authors wanted to get some more specific data.

Human genome editing can be used for two broad purposes: therapy or enhancement. Therapeutic applications include the treatment of genetic disorders like muscular dystrophy or sickle cell disease, while enhancement might be used to change your daughters eye color or make her grow taller.

Each of these changes can be heritable or not, depending on which type of cell is tweaked. Somatic cells are nonreproductive, so any changes to these cells will not be passed on to future generations. Germline cells, on the other hand, are heritable therefore, any modifications will be inherited by the treated persons children and grandchildren.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the acceptance of gene editing by application.

A graphic from the paper showing the acceptance of gene editing by application. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The new poll shows that two-thirds of Americans support therapeutic applications, whether to somatic (64% support) or germline (65% support) cells. When it comes to enhancement, however, there is much less approval. Only 39% of respondents find somatic enhancement acceptable, with 35% saying it is unacceptable. Levels of support dropped even lower for heritable germline enhancement, to 26% in acceptance and 51% in opposition.

When these results were broken down by how religious respondents were, some variation emerged. Religious people are less supportive of genome editing overall. Only half of them expressed some support of treatment applications, compared with 75% of nonreligious respondents. When it comes to enhancement, 28% of religious respondents and 45% of nonreligious people reported some level of support.

The authors also ranked respondents in terms of low, medium and high knowledge by their score on a nine-question factual quiz. Those in the high-knowledge category were far more supportive of treatment applications, with 76% in support compared with only 32% of low-knowledge respondents.

When asked about enhancement applications, the high-knowledge group was very polarized, with 41% in support and a nearly equal amount in opposition. In contrast, half of low-knowledge people reported that they neither support nor oppose gene editing.

Robert Blendon, who studies health policy at the Harvard School of Public Health, said that the polarization could be there for a reason. Those who know more about the technology have probably learned about it because they have a vested interest maybe a genetic disease runs in their family or they are concerned with ethical consequences.

Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge.

A graphic from the paper showing the opinions of respondents based on religiosity and knowledge. (Reprinted with permission from D.A. Scheufele et al., Science 357:6351 2017)

The more religious people were, the less likely they were to trust the scientific community to responsibly develop new technologies. This trend was opposite when it came to knowledge: The more knowledgeable people were about the technology, the more likely they were to trust the scientists.

While the two groups may have very different reasons, both highly religious and highly knowledgeable people agreed that the public should be involved in decision-making before gene editing is used in humans.

Blendon said that while its clear the public wants a say in how gene editing is used, its unclear exactly what public engagement looks like. The first way most people might think of being consulted is through their elected officials, but other surveys suggest that the public actually doesnt think the government should be making decisions about genome technology.

Scheufele said that there is currently no infrastructure in place for crucial two-way communication between scientists and the public on the genome editing issue but its important to develop it.

Diverse groups and perspectives have an important role to play in shaping the early stages of human genome editing research, Scheufele said. Scientists may not think to investigate all the questions that the public may deem vital.

If we ask the wrong questions, he said, then we may have perfect technical answers to all the wrong questions.

mira.abed@latimes.com

@mirakatherine

See the original post here:
Americans want a say in human genome editing, survey shows - Los Angeles Times

MoU signed to commercialise gene therapy in India – Odisha Sun Times

New Delhi: In a bid to advance research and commercialise regenerative medicine and gene therapy in India, the Association of Biotechnology Led Enterprise (ABLE) a consortium of biotechnology companies on Friday signed a Memorandum of Understanding (MoU) with a Japan-based trade association.

The collaboration between ABLE and Forum for Innovative Regenerative Medicine (FIRM) will focus on advancing the individual and common missions by sharing information including technology, policy and laws partnerships and opportunities such as co-sponsoring meetings and other cooperation based on common concern.

It will also help advance and promote commercialisation of life saving products in regenerative medicine within India, Japan and other countries.

We are proud to be a partner in this revolutionary research and industry collaborations. The partnership is a step forward to enhance the learning and training on cell and gene treatment leading to enhancement of the cell and gene therapies which help to address major unmet medical needs in India, P. Manohar, Head (Committee for regenerative medicine group) at ABLE, said in a statement on Friday.

Our association with ABLE is an opportunity to work towards the advancement of the field (of regenerative medicine and cell and gene therapies) and tap on the potential to transform human healthcare. Through the partnership, we can share learnings and insights to contribute towards curing major human illness, added Yuzo Toda, Chairman at FIRM. (IANS)

See original here:
MoU signed to commercialise gene therapy in India - Odisha Sun Times

Skin transplants could treat diabetes and obesity – Futurity: Research News

Skin transplantation could be an effective way to deliver gene therapy to treat type 2 diabetes and obesity, new research in mice suggests.

The technique could enable a wide range of gene-based therapies to treat many human diseases.

We think this can provide a long-term safe option for the treatment of many diseases

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, says study author Xiaoyang Wu, assistant professor in the cancer research department at the University of Chicago.

We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu says. It took us a few years to optimize our 3D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems.

We have a better than 80 percent success rate with skin transplantation, Wu says. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid.

Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors write.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu says. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive, and inexpensive.

There is also a need. More than 100 million US adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study are from the University of Chicago and the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society, and the V Foundation funded the study.

Source: University of Chicago

Follow this link:
Skin transplants could treat diabetes and obesity - Futurity: Research News

UCSD team adapts CRISPR to edit RNA for disease therapies – The San Diego Union-Tribune

UC San Diego researchers have invented a technology that offers a possible new way to fight genetic diseases, and have built a San Diego biotech company around their discovery.

The scientists adapted the powerful CRISPR/Cas9 DNA editing system, which has transformed the world of biology, to work on RNA, the messenger molecule that carries DNAs instructions into cells.

The system worked in cell cultures to stop production of RNA involved in forms of myotonic dystrophy, ALS and in Huntingtons disease. These are all incurable genetic diseases that can be fatal. This RNA can be toxic in itself, or produce abnormal proteins that cause disease.

About 95 percent of the disease-causing RNA was destroyed in the cell cultures.

The scientists have formed a San Diego biotech company called Locana to bring the technology to patients. Several years of development, including animal testing, is expected before that can happen.

The study was published Thursday in the journal Cell. Go to j.mp/rnacrispr to get the study. Gene Yeo was the senior author. The first authors were David Nelles and Ranjan Batra, postdoctoral researchers in Yeos lab.

CRISPR/Cas9 cuts DNA at specified targets, inactivating or altering gene sequences. It has been used for such feats like editing the genome of human embryos. The adapted system doesnt target the genome, but only RNA.

Scientists led by UC San Diegos Gene Yeo modified CRISPR so it doesnt target DNA and instead attacks specific RNA sequences, while leaving others alone. This specificity is vital for therapeutic purposes. It is delivered by an adenovirus, a virus commonly used in gene therapy.

The study expands on previous research that showed the RNA-adapted CRISPR could track RNA as it moves around cells. It didnt affect RNA production, however.

That study included Jennifer Doudna, a UC Berkeley scientist who helped pioneer the CRISPR system. Doudna is on Locanas scientific advisory board, Yeo said. He and Nelles are co-founders of Locana.

The Cas9 component, a protein that destroys the target, was too large to be delivered by the virus. So the team cut the proteins size by removing unnecessary parts used to cleave DNA. The result, RCas9, is guided by an accompanying RNA molecule to the target site.

Yeo said he expects the viral delivery system will remain effective for perhaps five to 10 years. Thats important because RNA is continually being produced from DNA, so the new disease-causing RNA must likewise be destroyed.

CRISPR star Jennifer Doudna calls for public debate on embryo editing

With embryo gene editing a reality, humanity enters a new era

Gene editing used to find cancer's genetic weak spots

DARPA funds UC gene drive research against mosquito-borne diseases

Can geneticists engineer healthier humans?

UCSD gene drive technology offers life-transforming power

bradley.fikes@sduniontribune.com

(619) 293-1020

Read the rest here:
UCSD team adapts CRISPR to edit RNA for disease therapies - The San Diego Union-Tribune

Drugmakers’ hopes for gene therapy rise despite tiny sales in Europe – Reuters

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's (QURE.O) Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's (GSK.L) Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics (ONCE.O) hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis (NOVN.S) could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio (BLUE.O), BioMarin (BMRN.O), Sangamo (SGMO.O) and GenSight (SIGHT.PA) - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer (PFE.N) and Sanofi (SASY.PA) are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire (SHP.L) CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Reporting by Ben Hirschler; editing by David Stamp

Read this article:
Drugmakers' hopes for gene therapy rise despite tiny sales in Europe - Reuters

Pfizer chooses Sanford, North Carolina site for $100m gene therapy plant – BioPharma-Reporter.com

Pfizer has chosen a site in Sanford, North Carolina for a gene therapy production plant, just 40 miles from its recent acquisition Bamboo Therapeutics Inc.

The US drug firm had been search for a site since March.

According to North Carolina Governor Roy Cooper, Pfizer will spend $100m (85m) on the new facility and has also committed $4m to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

The project will create jobs that deliver a total payroll impact of more than $3.9m each year to the community according to the North Carolina Department of Commerce and the Economic Development Partnership.

The project will be part funded by a $250,000 grant previously awarded to Wyeth which was acquired by Pfizer in 2009 - by the One North Carolina Fund, which helps local Governments attract economic investment.

Bamboo buy

The decision follows a little over a year after the US drug manufacturer acquired Bamboo Therapeutics, a North Carolina-based gene therapy developer.

The deal included a recombinant Adeno-Associated Virus (rAAV) vector design and production technology, a Phase I candidate for Giant Axonal Neuropathy and a preclinical programme targeting Duchenne Muscular Dystrophy (DMD).

Pfizer also gained a 11,000sq ft gene therapy manufacturing facility in Chapel Hill that Bamboo bought from the University of North Carolina in 2016.

See more here:
Pfizer chooses Sanford, North Carolina site for $100m gene therapy plant - BioPharma-Reporter.com

Pfizer investing $100M in Sanford plant expansion, adding jobs … – Triangle Business Journal


Triangle Business Journal
Pfizer investing $100M in Sanford plant expansion, adding jobs ...
Triangle Business Journal
Pfizer has confirmed plans to invest $100 million in the expansion of its Sanford research and manufacturing plant.

and more »

Follow this link:
Pfizer investing $100M in Sanford plant expansion, adding jobs ... - Triangle Business Journal

Silverstein-backed startup will test gene therapy for Parkinson’s – FierceBiotech

Regenxbio has joined forces with investment firm OrbiMed and a new nonprofit foundation to create Prevail Therapeutics, a startup focused on new biologics and gene therapiesfor Parkinson's disease (PD).

Prevail will draw on the expertise of the Silverstein Foundation for Parkinson's with GBA, which concentrates on a particular form of the disease caused by mutations in the glucocerebrosidase gene.

The foundation was set up this year by OrbiMed's co-head of private equity Jonathan Silverstein, who was diagnosed with GBA-linked PD in February and is mobilizing efforts to discover a cure for the disease. Silverstein backed the foundation with $10 million of his own money, and is intent on accelerating research into PD with GBA as well as other forms of the disease.

Prevail says it will focus initially on research coming out of the lab of its co-founder and CEO Asa Abeliovich, M.D., Ph.D., who is on the faculty of Columbia University as well as being a scientific adviser to the Silverstein Foundation and co-founder of neurodegenerative disease biotech Alector.

By joining forces with Regenxbio, Prevail launches with an exclusive license to the gene therapy specialist's adeno-associated virus (AAV) based vector technology NAV AAV9 for PD and other neurodegenerative disorders.

Silverstein said that the NAV platform and Dr. Abeliovich's "deep expertise in the molecular mechanisms of neurodegeneration provides us with a promising opportunity to develop potential life-changing therapies for patients suffering from Parkinson's disease and other neurodegenerative diseases."

He told CNBC today that Prevail's board will also have some big names, including Leonard Bell, co-founder and former CEO of Alexion, OrbiMed venture partner and Alexion co-founder Steve Squinto and serial entrepreneur Peter Thompson of Silverback Therapeutics and Corvus Pharmaceuticals.

The new company will initially focus on GBA1, the most common of the PD mutations, which is estimated to be present in up to 10% of U.S. PD patients and perhaps 100,000 people worldwide. The disease mechanism linked to the mutationan accumulation of alpha-synuclein in the brainmay have implications for the broader PD population and other neurodegenerative diseases.

"Many of the drugs we are trying for Parkinson's with GBA may work in the broader Parkinson's population," said Silverstein. The aim will be to get drugs approved for use in GBA patients first, and then expand their use into other patient groups.

The work of the foundation is attracting investment from companies who are not even active in PD, with cancer specialist Celgene today pledging a grant of $5 million.

Read more from the original source:
Silverstein-backed startup will test gene therapy for Parkinson's - FierceBiotech

Pfizer to invest $100M in Sanford gene therapy operation, add jobs … – WRAL Tech Wire

Updated Aug. 8, 2017 at 7:02 a.m.

Published: 2017-08-07 16:07:00 Updated: 2017-08-08 07:02:05

Sanford, N.C. Pharmaceutical giant Pfizer Inc. plans to invest $100 million in its Sanford operations as part of a push into gene therapy, officials said Monday.

The effort builds on a technology developed at the University of North Carolina at Chapel Hill and will create 40 jobs in Sanford.

"Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy," Lynn Bottone, site leader at Pfizer Sanford, said in a statement. "We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility."

Preliminary work on the expansion and initial hiring have already begun. The 230-acre campus employs about 450 people, reports the N.C. Biotechnology Center.

Gene therapy is a potentially transformational technology for patients that involves highly specialized, one-time treatments to address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Last year, Pfizer acquired Bamboo Therapeutics Inc., a privately held biotechnology company in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

"We are excited that Carolinas research will improve lives and create jobs for North Carolinians," UNC-Chapel Hill Chancellor Carol Folt said in a statement. "This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina, and we look forward to continue to help advance this industry."

Pfizer is also expanding a drug-manufacturing facility in Rocky Mount that it acquired from Hospira in 2015. The $190 million project will add 65,000 square feet of sterile injectable facilities but will not create any new jobs. The plant employs about 300 people.

Gov. Roy Cooper visited Pfizers Sanford facility last week to take a tour and meet with the companys senior leaders.

"North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line," Cooper said in a statement. "Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward."

Pfizer qualified for a performance-based grant of $250,000 from the One North Carolina Fund, which provides state assistance matched by local governments to help attract economic investment and create jobs. Companies receive no money upfront and must meet job and investment targets to obtain payment.

WRAL TechWire any time: Twitter, Facebook

Read more from the original source:
Pfizer to invest $100M in Sanford gene therapy operation, add jobs ... - WRAL Tech Wire

Pfizer Inc. Expands Biopharmaceutical Research Center in Sanford, North Carolina – Area Development Online

Related ResearchPfizer Inc., one of the worlds premier biopharmaceutical companies, will expand its research-production facilities in Sanford, North Carolina. The company will prepare to produce new gene therapy medicines.

Governor Roy Cooper announced the company plans to invest $100 million in its research facility in Lee County, creating 40 jobs and building upon a technology first developed at the University of North Carolina at Chapel Hill.

The Pfizer expansion in Sanford will focus on gene therapy, a potentially transformational technology for patients, focused on highly specialized, one-time treatments that address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy, states Lynn Bottone, Site Leader at Pfizer Sanford. We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility.

As an incentive a performance-based grant of $250,000 from the One North Carolina Fund will help facilitate Pfizers expansion in Lee County. The One NC grant will formally be awarded to Wyeth Holdings, LLC, a wholly-owned subsidiary of Pfizer Inc.

The One NC Fund provides financial assistance to local governments to help attract economic investment and to create jobs. Companies receive no money upfront and must meet job creation and capital investment targets to qualify for payment. All One NC grants require a matching grant from local governments and any award is contingent upon that condition being met.

North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line, Governor Cooper said. Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward.

In 2016, the company acquired Bamboo Therapeutics, Inc., a privately held biotechnology company based in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

Innovation drives economic opportunity and expansion, said North Carolina Commerce Secretary Anthony M. Copeland. Pfizers decision to expand in North Carolina proves how our investments in education pay off in new jobs and new solutions to the worlds toughest challenges.

We are excited that Carolinas research will improve lives and create jobs for North Carolinians, said Carol Folt, Chancellor of the University of North Carolina at Chapel Hill. This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina and we look forward to continue to help advance this industry.

The North Carolina Department of Commerce and the Economic Development Partnership of N.C. (EDPNC) were instrumental in supporting the companys investment decision. In addition to North Carolina Commerce and the Economic Partnership of North Carolina, other key partners in the project include the North Carolina General Assembly, the North Carolina Community College System, the University of North Carolina at Chapel Hill, the North Carolina Biotechnology Center, Duke Energy, Lee County, and the Sanford Area Growth Alliance.

Go here to see the original:
Pfizer Inc. Expands Biopharmaceutical Research Center in Sanford, North Carolina - Area Development Online

Gene Therapy Is Now Available, but Who Will Pay for It? – Scientific American

By Ben Hirschler

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

More here:
Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

Agilis Biotherapeutics and Gene Therapy Research Institution Enter … – Business Wire (press release)

CAMBRIDGE, Mass. & TOKYO--(BUSINESS WIRE)--Agilis Biotherapeutics, Inc. (Agilis), a biotechnology company advancing innovative DNA therapeutics for rare genetic diseases that affect the central nervous system (CNS), and Gene Therapy Research Institution Co, Ltd. (GTRI), a corporation with the mission of developing and delivering of the safest and most efficient gene therapies, today announced that the companies have completed a manufacturing and collaboration partnership joint venture (JV) to advance adeno-associated virus (AAV) gene therapies. The JV was initiated earlier this year in connection with a grant from the Japanese Ministry of Trade, Economics and Industry (METI) and Japan External Trade Organization (JETRO) for the development of a state-of-the-art AAV manufacturing facility in Japan. GTRI was co-founded by Professor Shin-ichi Muramatsu, M.D., a leading pioneer in gene therapy who has performed basic science and clinical research in the field for over two decades.

The JV, headquartered in Japan, will initially focus on developing and manufacturing AAV gene therapy vectors using Sf9 baculovirus and HEK293 mammalian cell systems and operate a process development and production facility located in the Tokyo area designed to meet international manufacturing standards, including cGMP, GCTP and PIC/S GMP requirements. Agilis and GTRI will also collaborate to expedite the development, approval and commercialization of select gene therapies in specific CNS diseases. Terms of the joint venture were not disclosed.

We are pleased to collaborate with Agilis to leverage each organizations capabilities and know-how, advance the manufacturing state-of-the art for gene therapy, and develop novel gene therapies, commented Katsuhito Asai, Chief Executive Officer of GTRI and a Director of the joint venture. Our partnership will seek to capitalize on the strong recent progress in the field of gene therapy and expedite the development of innovative gene therapies for patients in need, with a major emphasis on the quality production of safe, effective therapeutics.

We are thrilled to partner with GTRI, said Mark Pykett, Agilis CEO and a Director of the joint venture. We believe that our partnership will enhance the efforts of both organizations, build important shared production capabilities, and accelerate development and commercialization of important gene therapies. We look forward to working with GTRI on a range of initiatives.

Agilis Biotherapeutics

Agilis is advancing innovative gene therapies designed to provide long-term efficacy for patients with debilitating, often fatal, rare genetic diseases that affect the central nervous system. Agilis gene therapies are engineered to impart sustainable clinical benefits by inducing persistent expression of a therapeutic gene through precise targeting and restoration of lost gene function to achieve long-term efficacy. Agilis rare disease programs are focused on gene therapy for AADC deficiency, Friedreichs ataxia, and Angelman syndrome, all rare genetic diseases that include neurological deficits and result in physically debilitating conditions.

We invite you to visit our website at http://www.agilisbio.com

About GTRI

GTRI, a bio-tech venture in Japan, was founded in May 2014 based on the pioneering research of Dr. Shin-ichi Muramatsu, focusing on gene therapy using AAV vector as the leading company in Japan in this field. Its pipeline includes more than 20 diseases, targeting CNS diseases and monogenic disorders, such as Parkinsons disease, AADC deficiency, ALS, Alzheimers disease, spinocerebellar degeneration, Tay-Sachs disease, GLUT1 deficiency, and others.

Dr. Muramatsu, PhD, MD, of Jichi Medical University, is one of the top researchers of AAV vectors and AAV-mediated gene therapy in the world. He originated AAV3 in 1995 during his research at the NIH, USA, and afterwards developed his original modified AAV3/9 in Japan, which enables to deliver the gene of interest effectively in CNS through the blood-brain barrier.

Safe Harbor Statement

Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon our current expectations and projections about future events and generally relate to our plans, objectives and expectations for the development of our business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release.

Go here to read the rest:
Agilis Biotherapeutics and Gene Therapy Research Institution Enter ... - Business Wire (press release)

Cardiovascular disease cure? One session of THIS could help treat condition – Express.co.uk

Coronary heart disease is the term that describes what happens when the heart's blood supply is blocked or interrupted by a build-up of fatty substances in the coronary arteries.

This is a process called atherosclerosis.

Coronary heart disease can't be cured yet but treatment can help manage the symptoms and reduce the chances of problems such as heart attacks.

However, now experts have found a new gene therapy which targets the heart and requires only one treatment session.

The treatment has been found safe for patients with coronary artery disease, according to a successful trial carried out in Finland.

It works by enhancing circulation in the oxygen-deficient heart muscle and experts said the effects were visible even one year after the treatment.

A trial was carried out in collaboration between the University of Eastern Finland, Kuopio University Hospital and Turku PET Centre as part of the Centre of Excellence in Cardiovascular and Metabolic Diseases of the Academy of Finland.

The biological bypass is based on gene transfer in which a natural human growth hormones - called a factor - is injected into the heart muscle to enhance vascular growth.

The trial was the first in the world to use a vascular growth factor which has several beneficial effects on circulation in the heart muscle.

Experts also developed a precise method for injecting the gene into the oxygen-deficient heart muscle area.

A customised catheter is inserted via the patients groin vessels to the left ventricle, after which the gene solution can be injected directly into the heart muscle.

The method is as easy to perform as coronary balloon angioplasty, which means that it is also suitable for older patients and patients who are beyond a bypass surgery or other demanding surgical or arterial operations.

Experts said the biological bypass constitutes a significant step forward in the development of novel biological treatments for patients with severe coronary artery disease.

A new blood test biomarker was also discovered, making it possible to identify patients who are most likely to benefit from the new treatment.

The biological bypass was developed by a research group at the University of Eastern Finland.

Experts said research into the biological bypass will continue with a new trial set to start in 2018.

This trial will also include five other cardiology clinics from Denmark, the UK, Austria, Spain and Poland.

This comes after it was revealed heart disease risk could be determined by your waist size.

Go here to see the original:
Cardiovascular disease cure? One session of THIS could help treat condition - Express.co.uk

Human embryos ‘edited’ from potentially fatal gene mutation – Jordan Times

Using a powerful gene-editing technique, scientists have rid human embryos of a mutation that causes an inherited form of heart disease often deadly to healthy young athletes and adults in their prime.

The experiment marks the first time that scientists have altered the human genome to ensure a disease-causing mutation would disappear not only from the DNA of the subject on which its performed, but from the genes of his or her progeny as well.

The controversial procedure, known as germ-line editing, was conducted at Oregon Health & Science University using human embryos expressly created for the purpose. It was reported in the journal Nature.

The new research comes less than six months after the National Academies of Science, Engineering and Medicine recommended that scientists limit their trials of human germ-line editing to diseases that could not be treated with reasonable alternatives at least for now.

In a bid to make the experiment relevant to real-life dilemmas faced by parents who carry genes for inherited diseases, the researchers focused their editing efforts on a mutation that causes inherited hypertrophic cardiomyopathy.

In this genetic condition, a parent who carries one normal and one faulty copy of a the MYBPC3 gene has a 50-50 chance of passing that mutation on to his or her offspring. If the child inherits the mutation, his or her heart muscle is likely to grow prematurely weak and stiff, causing heart failure and often early death.

In diseases where one parent carries such an autosomal dominant mutation, a couple will often seek the assistance of fertility doctors to minimise the risk of passing such a mutation on to a child. A womans egg production is medically stimulated, and eggs and sperm meet in a lab a process called in vitro fertilisation. Then embryologists inspect the resulting embryos, cull the ones that have inherited an unwanted mutation, and transfer only unaffected embryos into a womans uterus to be carried to term.

In the new research, researchers set out to test whether germ-line gene editing could make the process of choosing healthy embryos more effective and efficient by creating more of them.

In the end, their experiment showed it could. The targeted correction of a disease-causing gene carried by a single parent can potentially rescue a substantial portion of mutant human embryos, thus increasing the number of embryos available for transfer, the authors wrote in Nature. Co-author Dr Paula Amato, an Oregon Health & Science University (OHSU) professor of obstetrics and gynaecology, said the technique could potentially decrease the number of cycles needed for people trying to have children free of genetic disease if its found safe for use in fertility clinics.

Along the way, though, many of the researchers findings were scientifically surprising. Long-feared effects of germ-line editing, including collateral damage to off-target genetic sequences, scarcely materialised. And mosaicism, a phenomenon in which edited DNA appears in some but not all cells, was found to be minimal.

The studys lead author, OHSU biologist Shoukhrat Mitalipov, called these exciting and surprising moments. But he cautioned that there is room to improve the techniques demonstrated to produce mutation-free embryos. As for conducting human clinical trials of the germ-line correction, he said those would have to wait until results showed a near-perfect level of efficiency and accuracy, and could be limited by state and federal regulations.

Eventually, Mitalipov said, such germ-line gene editing might also make it easier for parents who carry other gene mutations that follow a similar pattern of inheritance including some that cause breast and ovarian cancers, cystic fibrosis and muscular dystrophy to have healthy children who would not pass those genes to their own offspring.

There is still a long road ahead, predicted Mitalipov, who heads the Centre for Embryonic Cell and Gene Therapy at the Portland university.

The research drew a mix of praise and concern from experts in genetic medicine.

Dr Richard O. Hynes, who co-chaired the National Academies report issued in February, called the new study very good science that advances understanding of genetic repair on many fronts. Hynes, who was not involved with the latest research effort, said he was pleasantly surprised by researchers clever modifications and their outcomes.

Its likely to become feasible, technically not tomorrow, not next year, but in some foreseeable time. Less than a decade, Id say, said Haynes, a biologist and cancer researcher at MIT and the Howard Hughes Medical Institute.

University of California, Berkeley molecular and cell biologist Jennifer Doudna, one of pioneers of the CRISPR-Cas9 gene-editing technique, acknowledged the new research highlights a prospective use of gene editing for one inherited disease and offers some insights into the process.

But Doudna questioned how broadly the experiments promising results would apply to other inherited diseases. She said she does not believe the use of germ-line editing as a means to improve efficiency at infertility clinics meets the criteria laid out by the National Academies of Science, which urged that the techniques only be explored as treatment for diseases with no reasonable alternative.

Already, 50 per cent of embryos would be normal, said Doudna. Why not just implant those?

Doudna said she worried that the new findings will encourage people to proceed down this road before the scientific and ethical implications of germ-line editing have been fully considered.

A large group of experts concluded that clinical use should not proceed until and unless theres broad societal consensus, and that just hasnt happened, Doudna said. This study underscores the urgency of having those debates. Because its coming.

Read the original post:
Human embryos 'edited' from potentially fatal gene mutation - Jordan Times

Agilis Biotherapeutics, Gene Therapy Research Institution Enter Strategic Partnership – Drug Discovery & Development

Agilis Biotherapeutics, Inc. (Agilis), a biotechnology company advancing innovative DNA therapeutics for rare genetic diseases that affect the central nervous system (CNS), and Gene Therapy Research Institution Co, Ltd. (GTRI), a corporation with the mission of developing and delivering of the safest and most efficient gene therapies, announced that the companies have completed a manufacturing and collaboration partnership joint venture (JV) to advance adeno-associated virus (AAV) gene therapies. The JV was initiated earlier this year in connection with a grant from the Japanese Ministry of Trade, Economics and Industry (METI) and Japan External Trade Organization (JETRO) for the development of a state-of-the-art AAV manufacturing facility in Japan. GTRI was co-founded by Professor Shin-ichi Muramatsu, M.D., a leading pioneer in gene therapy who has performed basic science and clinical research in the field for over two decades.

The JV, headquartered in Japan, will initially focus on developing and manufacturing AAV gene therapy vectors using Sf9 baculovirus and HEK293 mammalian cell systems and operate a process development and production facility located in the Tokyo area designed to meet international manufacturing standards, including cGMP, GCTP and PIC/S GMP requirements. Agilis and GTRI will also collaborate to expedite the development, approval and commercialization of select gene therapies in specific CNS diseases. Terms of the joint venture were not disclosed.

We are pleased to collaborate with Agilis to leverage each organizations capabilities and know-how, advance the manufacturing state-of-the art for gene therapy, and develop novel gene therapies, commented Katsuhito Asai, Chief Executive Officer of GTRI and a Director of the joint venture. Our partnership will seek to capitalize on the strong recent progress in the field of gene therapy and expedite the development of innovative gene therapies for patients in need, with a major emphasis on the quality production of safe, effective therapeutics.

We are thrilled to partner with GTRI, said Mark Pykett, Agilis CEO and a Director of the joint venture. We believe that our partnership will enhance the efforts of both organizations, build important shared production capabilities, and accelerate development and commercialization of important gene therapies. We look forward to working with GTRI on a range of initiatives.

View post:
Agilis Biotherapeutics, Gene Therapy Research Institution Enter Strategic Partnership - Drug Discovery & Development

Researchers Are Finding Remarkable Ways to Combat Aging and Extend Human Health – Futurism

In BriefThis is truly the golden age of anti-aging research, with extended telemores, senescent cell therapies, and young-blood transfusions being three of the most promising treatment avenues. However, even if one of these therapies proves to be the proverbial "fountain of youth," the financial cost of a long, healthy life is still well out of reach for most people.

The idea of never growing old is seductive, but it has remained a pipe-dream throughout history. However, that may not be the case for much longer as the scientific community has seen a surge in anti-aging research in recent years.All across the globe, researchers are now exploring different methods to combat aging and extend human health span (the number of years of good health a person experiences).

The avenue that is arguably generating the most support involves telemores. These are the caps that sit on the ends of chromosomes. They provide protection for the DNA molecules, and their length has been linked to good health. Unfortunately, they shrinkwith every division until they can no longer protect the cell and it dies or damages surrounding cells through senescence.

So far, the research on telemores has been promising.Maria Blasco of the Spanish National Cancer Research Centre used gene therapy to extendthe telemores in mice, which led to a 40 percent increase in lifespan.

Meanwhile Helen Blau, Director of the Baxter Laboratory for Stem Cell Biology at Stanford, modified the RNA of skin cells to increase telemore length. This caused the cells to divide up to 40 moretimes than their untreated counterparts did before dying or stagnating.

Another promising avenue of anti-aging research involved targeting senescent cells. These cells pump out chemicals as they deteriorate that are damaging to their neighboring cells, causing many of the diseases associated with aging, so researchers have been looking for ways to either inhibit their development or periodically purge them.

At the Mayo Clinic in Rochester, Minnesota,Darren Bakerand his colleagues found that giving mice a drug that destroyed these cells delayed the development of the diseases of aging, as well as made the mice look plumper and younger.

At the slightly more unsettlingend of the anti-aging treatment spectrum is the process of transfusing the blood of the young into the old. Despite the vampiric and macabre nature of the treatment, researchers have found evidence that it is effective. Individuals who receive blood from younger donors report health benefits, such as lowered cholesterol levels, while older mice have been shown to be rejuvenated by injections of blood from younger mice or evenhuman teenagers.

While science is movingquickly toward a future in which aging and its consequences are obsolete, the few commercial means of receiving the treatments above are, at present, extremely expensive.

Liz Parrishis not a biologist by training, but she did enlist the help of scientists to develop the telemore-based treatment offered by her company,BioViva. Ostensibly, Parrish has developed an injection based on Blancos principles, andshe herself is patient zero, having already injected herself with that telomere-extending treatment as well as one designed to preserve muscle mass. While BioVivahasnt gone to market yet, Parrish told New Humanist that eachinjection costs between $200,000 to $400,000 to produce.

While no commercial means of senescent cell therapy exists as of yet, individuals can buy young blood transfusions. Jesse Karmazins company Ambrosia offers blood plasma transfusions for anyone willing to pay $8,000.

However, Stanford University neuroscientist Tony Wyss-Coray, who has conducted numerous experiments on mices reaction to young blood, thinks youd be better off saving your money. He dismisses the science behind the treatment,telling MIT Technology Review that people want to believe that young blood restores youth, even though we dont have evidence that it works in humans.

For the moment, anti-aging therapies are attainable in theory, but well out of financial reach for all except a wealthy few. Once the science is crystallized, however, the treatments should become exponentially cheaper, and a long, healthy life will be neither a pipe dream nor a hideously expensive commodity.

Read this article:
Researchers Are Finding Remarkable Ways to Combat Aging and Extend Human Health - Futurism

Genome editing and the AMA Code of Medical Ethics – American Medical Association (blog)

An international team of researchers recently published, in the journal Nature, their study using genome editing to correct a heterozygous mutation in human preimplantation embryos using a technique called CRISPR-Cas9. This bench research, while far from bedside use, raises questions about the medical ethics of what could be considered genetic engineering. The AMA Code of Medical Ethics has guidance for physicians conducting research in this area.

In Opinion 7.3.6, Research in Gene Therapy and Genetic Engineering, the Code explains:

Gene therapy involves the replacement or modification of a genetic variant to restore or enhance cellular function or the improve response to nongenetic therapies. Genetic engineering involves the use of recombinant DNA techniques to introduce new characteristics or traits. In medicine, the goal of gene therapy and genetic engineering is to alleviate human suffering and disease. As with all therapies, this goal should be pursued only within the ethical traditions of the profession, which gives primacy to the welfare of the patient.

In general, genetic manipulation should be reserved for therapeutic purposes. Efforts to enhance desirable characteristics or to improve complex human traits are contrary to the ethical tradition of medicine. Because of the potential for abuse, genetic manipulation of nondisease traits or the eugenic development of offspring may never be justifiable.

Moreover, genetic manipulation can carry risks to both the individuals into whom modified genetic material is introduced and to future generations. Somatic cell gene therapy targets nongerm cells and thus does not carry risk to future generations. Germ-line therapy, in which a genetic modification is introduced into the genome of human gametes or their precursors, is intended to result in the expression of the modified gene in the recipients offspring and subsequent generations. Germ-line therapy thus may be associated with increased risk and the possibility of unpredictable and irreversible results that adversely affect the welfare of subsequent generations.

Thus, in addition to fundamental ethical requirements for the appropriate conduct of research with human participants, research in gene therapy or genetic engineering must put in place additional safeguards to vigorously protect the safety and well-being of participants and future generations.

Physicians should not engage in research involving gene therapy or genetic engineering with human participants unless the following conditions are met:

(a) Participate only in those studies for which they have relevant expertise.

(b) Ensure that voluntary consent has been obtained from each participant or from the participants legally authorized representative if the participant lacks the capacity to consent, in keeping with ethics guidance. This requires that:

(i) prospective participants receive the information they need to make well-considered decisions, including informing them about the nature of the research and potential harms involved;

(ii) physicians make all reasonable efforts to ensure that participants understand the research is not intended to benefit them individually;

(iii) physicians also make clear that the individual may refuse to participate or may withdraw from the protocol at any time.

(c) Assure themselves that the research protocol is scientifically sound and meets ethical guidelines for research with human participants. Informed consent can never be invoked to justify an unethical study design.

(d) Demonstrate the same care and concern for the well-being of research participants that they would for patients to whom they provide clinical care in a therapeutic relationship. Physician researchers should advocate for access to experimental interventions that have proven effectiveness for patients.

(e) Be mindful of conflicts of interest and assure themselves that appropriate safeguards are in place to protect the integrity of the research and the welfare of human participants.

(f) Adhere to rigorous scientific and ethical standards in conducting, supervising, and disseminating results of the research.

AMA Principles of Medical Ethics: I,II,III,V

At the 2016 AMA Interim Meeting, the AMA House of Delegates adopted policy on genome editing and its potential clinical use. In the policy, the AMA encourages continued research into the therapeutic use of genome editing and also urges continued development of consensus international principles, grounded in science and ethics, to determine permissible therapeutic applications of germline genome editing.

Chapter 7 of the Code, Opinions on Research & Innovation, also features guidance on other research-related subjects, including informed consent, conflicts of interest, use of placebo controls, and the use of DNA databanks.

The Code of Medical Ethics is updated periodically to address the changing conditions of medicine. The new edition, adopted in June 2016, is the culmination of an eight-year project to comprehensively review, update and reorganize guidance to ensure that the Code remains timely and easy to use for physicians in teaching and in practice.

Here is the original post:
Genome editing and the AMA Code of Medical Ethics - American Medical Association (blog)

Gene therapy cancer treatment funded by Stamford nonprofit awaits FDA approval – Westfair Online

Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci and President and CEO John E. Walter outside the nonprofits headquarters in Stamford. Photo by Phil Hall.

The development of an experimental gene-targeting therapy in cancer treatment that could be approved for the U.S. market this year was sparked in large part by the research funding support of a Stamford nonprofit.

The chimeric antigen receptor T-cell (CAR-T) drug, labeled tisagenlecleucel by its manufacturer, Novartis, in July was unanimously recommended for approval by the oncologic drugs advisory committee of the U.S. Food and Drug Administration. If the FDA grants final approval as expected this fall, it will be the first drug treatment targeting human genes approved for the U.S. market.

In Stamford, the Alliance for Cancer Gene Therapy since 2004 has provided a total of $1.8 million to Dr. Carl June at the University of Pennsylvania, the lead researcher in developing the CAR-T therapy. John E. Walter, president and CEO of the Stamford organization, said Junes work has helped to redefine perceptions of what gene therapy can accomplish.

Oftentimes, gene therapy is perceived as taking the bad genes out and putting some good genes in, Walter said. In this case, a patients T-cells are being removed and re-engineered with a virus and reintroduced in the body. With this genetic re-engineering, they become killer T-cells they go in and go after and kill the cancer cells.

Cancer cells in your body multiply and dont know how to die, said Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci. We have cells in our system all of the time that are growing and dying, but cancer cells dont do that. This therapy is for supercharging your own immune system to recognize these cancer cells and kill them.

If approved, the Novartis drug would mark a milestone achievement for the Alliance, whose creation in 2001 was driven by a tragic loss caused by cancer in its co-founders family. Edward Netter, chairman and CEO of Geneve Corp., a financial services holding company in Stamford, and his wife Barbara, a staff therapist at Pelham Family Services in Westchester County, lost their daughter-in-law, Kimberly Lawrence-Netter, to breast cancer. Edward Netter died from cancer in 2011. His wife serves as the nonprofits honorary board chairwoman.

Walter, who served as CEO of the Leukemia & Lymphoma Society before joining the Alliance in May 2016, noted that this organization differed from most because all of its raised funds are used solely to finance research. Our administrative expenses are paid for by our board and by the Netters, he said, and the nonprofits four-person staff works out of Geneve Corp. headquarters. One hundred percent of your contributions go to research.

Since its founding, the Alliance has allocated approximately $29 million in grants to U.S. and Canadian projects. These are grants to two different types of scientists, said Cianci. We started funding young investigators at assistant professor level who have just become independent. It is difficult for them to get funding, especially in an area as innovative as gene therapy, and the government doesnt like to fund what they see as high-risk projects. We also fund clinical investigators, which included Dr. June.

The Alliance puts out two requests for funding applications each year, which are judged through a peer-review process coordinated by a scientific advisory committee.

There is always more research than there are dollars, said Walter. Invariably, we are leaving research on the table because we dont have the dollars to fund those.

The nonprofit itself receives funding through contributions from longtime donors and an annual fundraising event coordinated by Swim Across America that is held in the Long Island Sound directly across from its offices. That raises about $400,000 a year, Walter said.

Dr. Junes Alliance-funded research was published in a medical journal in 2011 in a study of three patients with advanced chronic lymphocytic leukemia. Novartis, the Swiss pharmaceutical company, expressed interest in the results and paid the University of Pennsylvania $20 million to license the technology.

Once we have survival data for these patients in Novartis-sponsored clinical trials, over time the FDA could consider using this as frontline treatment instead of highly toxic chemotherapy, said Walter.

For Cianci, the Alliances mission is crucial in encouraging new generations of researchers to focus on cancer and gene therapy solutions, especially when federal funding is being threatened by budget cuts.

If we dont fund the young scientists, they are going to leave the field, she warned. We dont want to lose some of these incredible minds. The average age for getting your first grant from the National Institute of Health is 42. What do you tell someone who just became a postdoctoral researcher and wants to have their own lab? How are they going to get funding?

One in four people could potentially get cancer in their lifetimes, Cianci said. And who hasnt been touched by cancer in one way or another?

Read more:
Gene therapy cancer treatment funded by Stamford nonprofit awaits FDA approval - Westfair Online

In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos – New York Times

Weve always said in the past gene editing shouldnt be done, mostly because it couldnt be done safely, said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. Thats still true, but now it looks like its going to be done safely soon, he said, adding that the research is a big breakthrough.

What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Nows the time.

Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells not just some were mutation-free, and they avoided creating unwanted extra mutations.

It feels a bit like a one small step for (hu)mans, one giant leap for (hu)mankind moment, Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.

Scientists tried two techniques to remove a dangerous mutation. In the first, genetic scissors were inserted into fertilized eggs. The mutation was repaired in some of the resulting embryos but not always in every cell. The second method worked better: By injecting the scissors along with the sperm into the egg, more embryos emerged with repaired genes in every cell.

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing components

inserted together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing

components inserted

together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

I expect these results will be encouraging to those who hope to use human embryo editing for either research or eventual clinical purposes, said Dr. Doudna, who was not involved in the study.

Much more research is needed before the method could be tested in clinical trials, currently impermissible under federal law. But if the technique is found to work safely with this and other mutations, it might help some couples who could not otherwise have healthy children.

Potentially, it could apply to any of more than 10,000 conditions caused by specific inherited mutations. Researchers and experts said those might include breast and ovarian cancer linked to BRCA mutations, as well as diseases like Huntingtons, Tay-Sachs, beta thalassemia, and even sickle cell anemia, cystic fibrosis or some cases of early-onset Alzheimers.

You could certainly help families who have been blighted by a horrible genetic disease, said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London, who was not involved in the study.

You could quite imagine that in the future the demand would increase. Maybe it will still be small, but for those individuals it will be very important.

The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves.

In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cells mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell.

We were so surprised that we just couldnt get this template that we made to be used, said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. It was very new and unusual.

The research significantly improves upon previous efforts. In three sets of experiments in China since 2015, researchers seldom managed to get the intended change into embryonic genes.

And some embryos had cells that did not get repaired a phenomenon called mosaicism that could result in the mutation being passed on as well as unplanned mutations that could cause other health problems.

In February, a National Academy of Sciences, Engineering and Medicine committee endorsed modifying embryos, but only to correct mutations that cause a serious disease or condition and when no reasonable alternatives exist.

Sheldon Krimsky, a bioethicist at Tufts University, said the main uncertainty about the new technique was whether reasonable alternatives to gene editing already exist.

As the authors themselves noted, many couples use pre-implantation genetic diagnosis to screen embryos at fertility clinics, allowing only healthy ones to be implanted. For these parents, gene editing could help by repairing mutant embryos so that more disease-free embryos would be available for implantation.

Hank Greely, director of the Center for Law and the Biosciences at Stanford, said creating fewer defective embryos also would reduce the number discarded by fertility clinics, which some people oppose.

The larger issue is so-called germline engineering, which refers to changes made to embryo that are inheritable.

If youre in one camp, its a horror to be avoided, and if youre in the other camp, its desirable, Dr. Greely said. Thats going to continue to be the fight, whether its a feature or a bug.

For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.)

The authors say they hope that once the method is optimized and studied with other mutations, officials in the United States or another country will allow regulated clinical trials.

I think it could be widely used, if its proven safe, said Dr. Paula Amato, a co-author of the study and reproductive endocrinologist at O.H.S.U. Besides creating more healthy embryos for in vitro fertilization, she said, it could be used when screening embryos is not an option or to reduce arduous IVF cycles for women.

Dr. Mitalipov has pushed the scientific envelope before, generating ethical controversy with a so-called three-parent baby procedure that would place the nucleus of the egg of a woman with defective cellular mitochondria into the egg from a healthy woman. The F.D.A. has not approved trials of the method, but Britain may begin one soon.

The new study involves hypertrophic cardiomyopathy, a disease affecting about one in 500 people, which can cause sudden heart failure, often in young athletes.

It is caused by a mutation in a gene called MYBPC3. If one parent has a mutated copy, there is a 50 percent chance of passing the disease to children.

Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.

They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.

Instead, the male gene copied the healthy sequence from the female gene. The authors dont know why it happened.

Maybe human sex cells or gametes evolved to repair themselves because they are the only cells that transmit genes to offspring and need special protection, said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Out of 54 embryos, 36 emerged mutation-free, a significant improvement over natural circumstances in which about half would not have the mutation. Another 13 embryos also emerged without the mutation, but not in every cell.

The researchers tried to eliminate the problem by acting at an earlier stage, injecting the egg with the sperm and CRISPR-Cas9 simultaneously, instead of waiting to inject CRISPR-Cas9 into the already fertilized egg.

That resulted in 42 of 58 embryos, 72 percent, with two mutation-free copies of the gene in every cell. They also found no unwanted mutations in the embryos, which were destroyed after about three days.

The method was not perfect. The remaining 16 embryos had unwanted additions or deletions of DNA. Dr. Mitalipov said he believed fine-tuning the process would make at least 90 percent of embryos mutation-free.

And for disease-causing mutations on maternal genes, the same process should occur, with the fathers healthy genetic sequence being copied, he said.

But the technique will not work if both parents have two defective copies. Then, scientists would have to determine how to coax one gene to copy a synthetic DNA sequence, Dr. Mitalipov said.

Otherwise, he said, it should work with many diseases, a variety of different heritable mutations.

R. Alta Charo, a bioethicist at University of Wisconsin at Madison, who led the committee with Dr. Hynes, said the new discovery could also yield more information about causes of infertility and miscarriages.

She doubts a flood of couples will have edited children.

Nobodys going to do this for trivial reasons, Dr. Charo said. Sex is cheaper and its more fun than IVF, so unless youve got a real need, youre not going to use it.

See original here:
In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos - New York Times

Archives