Archive for the ‘Gene Therapy Research’ Category

Have researchers taken a step closer to developing an eventual cure for HIV? A Temple University-led team hopes so, by using a gene editing technique to successfully remove HIV infection from lab mice. The gene-editing tool calledCRISPR which allows scientists to basically cut out and insert specific portions of DNA was used to excise HIV DNA from the mice.

This was the first time CRISPR has been used to shut down HIV replication and eliminate the virus from animal cells. Think of CRISPR as working somewhat like microscopic scissors that snip out an unwanted piece of DNA and then replace that with a new piece. The research, published in the journal Molecular Therapy, involved three animal models, including a "humanized" model where human immune cells infected with the virus were transplanted in lab mice.

"Over our years of research, all of this was frankly a big surprise. This research, so far, has yielded all pleasant surprises, frankly. I never thought that this CRISPR system was going to be working out so beautifully with such efficiency and precision when it first came onto the scene," Kamel Khalili, director of Temple's center for neurovirology, told CBS News.

Khalili led the study along with Wenhui Hu, associate professor in Temple University School of Medicine's Center for Metabolic Disease Research and the Department of Pathology, and Won-Bin Young, who was at that time an assistant professor in the Department of Radiology at the University of Pittsburgh School of Medicine.

This work builds off the team's previously published research last year in which they introduced the HIV-1 DNA into the tissue of rat and mice subjects, and then removed these fragments using CRISPR. This new study is the first time this has been done in three animal models.

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While the work signals progress, the medical community still sees years of work ahead before there's a reliable cure for HIV. According to the World Health Organization, 36.7 million people were reported to be living with HIV globally by the end of 2015. Since the start of the HIV/AIDS epidemic, more than 70 million people have been infected with the virus that has resulted in 35 million deaths.

The stakes are high, and the Temple team is one of many trying to find a cure for the virus, which has proven exceptionally difficult to eliminate from the body. While current drug treatments can reduce the virus to virtually undetectable levels enabling many patients to live longer, healthier lives HIV continues to lurk in hidden reservoirs and comes roaring back if treatment stops. In late 2015, theamfAR Institute for HIV Cure Research set the ambitious goal of developing a basis for cure for HIV by the end of 2020.

"The basic science community in HIV research is now very focused on finding a cure," Paul Voldberding, head of the institute, wrote in an email to CBS News. "It still feels a long way off but the tools we now have definitely including the gene editing used in this report is accelerating our work and raising optimism. The cure field is in very close contact and collaborations are active world wide. It's really quite exciting!"

Voldberding is also the director of the UCSF AIDS Research Institute and has a place in history for founding the first inpatient ward for people with AIDS at San Francisco General Hospital in 1983. How promising does he view this new research out of Temple?

"Gene editing is a potent and still rather new tool in HIV research and many other areas as well," he wrote. "It faces a challenge in scalability getting the technology simplified and inexpensive but is certainly worth following."

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Since first being developed a mere five years ago, CRISPR has generated excitement and controversy in equal measures. While it was named "Breakthrough of the Year" in 2015 by Science magazine, ethical debate has swirled around CRISPR over how it could be used for good or ill to make changes to our DNA down the line.

Ellen Jorgensen, a molecular biologist and science communicator whose latest project is the yet-to-launch Biotech Without Borders, said she thinks it's important to focus on the potential of CRISPR, rather than feed into the "hysteria" that can surround such life-altering scientific technologies.

"I think CRISPR is an example of why the general public should embrace the chance to learn more about this sort of technology that will be more and more relevant to everyone's daily life as time goes on," Jorgensen told CBS News. "We are in an age of biotechnology as opposed to the last century, which was the 'age of physics.' There is an equal potential here to disrupt technologies, but it also creates ethical questions that the general public has to weigh in on. My thing is, I want them to weigh in on them, but have the understanding that this technology is something that is powerful and that can spur a lot of change moving forward."

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In the case of this latest HIV research advance, Jorgensen, who cofounded Genspace, a nonprofit devoted to fostering better science literacy, said she believes there is "great potential" in finding a cure for something like HIV through gene editing technology.

Moving forward, Khalili and his team plan to try their technique on primate subjects, whose DNA is obviously closer to humans. He said they are working on securing more funding to move on to primate clinical trials.

Voldberding added that "primates are a very good model for human trials," and that research like this is promising in the continued fight against HIV.

"I think that CRISPR and tools like it are revolutionizing the medical field and will bring about new ways for the treatment and cure for a broad range of diseases," Khalili said. "When it comes to treating HIV or cancer or other genetic diseases, I think there are a lot of good things that will come out of this."

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Researchers use gene editing to eliminate HIV infection in mice - CBS News

Taube Philanthropies, founded by US-based Jewish businessman Tad Taube, said it would donate $3 million to support a collaboration between Stanford University School of Medicine and the Gladstone Institutes in California focused on research related to Huntingtons disease.

The donation will support a new program with three medical research groups and, for the first time, introduce gene editing and stem cell therapies for treatments and, eventually, a potential cure for Huntingtons disease, the philanthropic group said in a statement.

Researchers from Stanford School of Medicine and the Gladstone Institutes Taube-Koret Center for Neurodegenerative Disease Research, will collaborate with clinical trials at the Memory and Aging Center of the University of California, San Francisco (UCSF).

Huntingtons disease is a cruel genetic disorder that robs its victims of physical and mental control, said Taube, the chairman of Taube Philanthropies. The time and research that Stanford, UCSF and Gladstone Institutes have committed to this cause is remarkable.

Huntingtons disease is a genetic neurodegenerative disease that causes the progressive breakdown of nerve cells in the brain. It causes physical and mental abilities to deteriorate, eventually leading to premature death. There is no cure or approved drugs to slow the progression of the disorder. Huntingtons disease belongs to a family of neurodegenerative diseases that includes Alzheimers, Parkinsons and ALS. Today, there are approximately 30,000 symptomatic Americans and more than 200,000 at risk of inheriting the disease.

We have made considerable progress in advancing drug therapy developments for patients with neurodegenerative diseases since Taube Philanthropies started supporting my research, nearly a decade ago, said Dr. Steve Finkbeiner, director of the Gladstone Institutes Taube-Koret Center. With this renewed commitment and concerted approach focusing on Huntingtons disease, I am optimistic that we will continue advancing toward our research goals.

The $3 million donation is a continuation of Taube Philanthropies aim to finding treatments and cures for neurodegenerative diseases. Over the last 12 years, the organization has donated over $5 million to Gladstone Institutes and $1 million to the Stanford University School of Medicine for related research. Taube Philanthropies started funding Huntingtons disease research under the direction of Nobel laureate Dr. Stanley Prusiner at UCSFs department of neurology.

We have been working to develop similar therapies for neurodegenerative diseases for many years with some promising results, said Dr. Matthew Porteus, associate professor of pediatrics at Stanford. Employing the latest technology, including CRISPR/Cas9 a powerful new tool that enables scientists to make precise genome edits I believe we have the opportunity to make great strides toward developing a therapy specifically for Huntingtons disease.

The funds will be distributed to the researchers in annual payments through 2021, to account for the long-term process of translating scientific discoveries into clinical trials and applications. The research team will take on a multi-year program to develop genetic therapy for the disease. Stanford is already doing stem cell research and hopes to begin conducting clinical trials with Huntingtons patients soon, the statement said.

Having studied Alzheimers for many years, I am all too familiar with the devastating effects of neurodegenerative diseases, said Dr. Frank Longo, professor of neurology at Stanford. As researchers with different area specialties convene for this unique joint project, I am optimistic about our capacity to come even closer to finding treatments and cures for these degenerative conditions.

Research into Huntingtons disease has until recently suffered from a lack of significant funding. Due to the progress made in the field by researchers, new US federal funding has become available and major pharmaceutical companies have started funding research to develop possible medications. However, collaborative efforts still rely on contributions from individuals and private foundations, the statement said.

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Taube to fund $3m Huntington's disease research in US - The Times of Israel

Using the gene-editing system known as CRISPR, MIT researchers have shown in mice that they can generate colon tumors that very closely resemble human tumors. This advance should help scientists learn more about how the disease progresses and allow them to test new therapies.

Once formed, many of these experimental tumors spread to the liver, just like human colon cancers often do. These metastases are the most common cause of death from colon cancer.

"That's been a missing piece in the study of colon cancer. There is really no reliable method for recapitulating the metastatic progression from a primary tumor in the colon to the liver," says Omer Yilmaz, an MIT assistant professor of biology, a member of MIT's Koch Institute for Integrative Cancer Research, and the lead senior author of the study, which appears in the May 1 issue of Nature Biotechnology.

The study builds on recent work by Tyler Jacks, the director of the Koch Institute, who has also used CRISPR to generate lung and liver tumors in mice.

"CRISPR-based technologies have begun to revolutionize many aspects of cancer research, including building mouse models of the disease with greater speed and greater precision. This study is a good example of both," says Jacks, who is also an author of the Nature Biotechnology paper.

The paper's lead authors are Jatin Roper, a research affiliate at the Koch Institute and a gastroenterologist at Tufts Medical Center, and Tuomas Tammela, a research scientist at the Koch Institute.

Mimicking human tumors

For many years, cancer biologists have taken two distinct approaches to modeling cancer. One is to grow immortalized human cancer cells known as cancer cell lines in a lab dish. "We've learned a lot by studying these two-dimensional cell lines, but they have limitations," Yilmaz says. "They don't really reproduce the complex in vivo environment of a tumor."

Another widely used technique is genetically engineering mice with mutations that predispose them to develop cancer. However, it can take years to breed such mice, especially if they have more than one cancer-linked mutation.

Recently, researchers have begun using CRISPR to generate cancer models. CRISPR, originally discovered by biologists studying the bacterial immune system, consists of a DNA-cutting enzyme called Cas9 and short RNA guide strands that target specific sequences of the genome, telling Cas9 where to make its cuts. Using this process, scientists can make targeted mutations in the genomes of living animals, either deleting genes or inserting new ones.

To induce cancer mutations, the investigators package the genes for Cas9 and the RNA guide strand into viruses called lentiviruses, which are then injected into the target organs of adult mice.

Yilmaz, who studies colon cancer and how it is influenced by genes, diet, and aging, decided to adapt this approach to generate colon tumors in mice. He and members of his lab were already working on a technique for growing miniature tissues known as organoids -- three-dimensional growths that, in this case, accurately replicate the structure of the colon.

In the new paper, the researchers used CRISPR to introduce cancer-causing mutations into the organoids and then delivered them via colonoscopy to the colon, where they attached to the lining and formed tumors.

"We were able to transplant these 3-D mini-intestinal tumors into the colon of recipient mice and recapitulate many aspects of human disease," Yilmaz says.

More accurate modeling

Once the tumors are established in the mice, the researchers can introduce additional mutations at any time, allowing them to study the influence of each mutation on tumor initiation, progression, and metastasis.

Almost 30 years ago, scientists discovered that colon tumors in humans usually acquire cancerous mutations in a particular order, but they haven't been able to accurately model this in mice until now.

"In human patients, mutations never occur all at once," Tammela says. "Mutations are acquired over time as the tumor progresses and becomes more aggressive, more invasive, and more metastatic. Now we can model this in mice."

To demonstrate that ability, the MIT team delivered organoids with a mutated form of the APC gene, which is the cancer-initiating mutation in 80 percent of colon cancer patients. Once the tumors were established, they introduced a mutated form of KRAS, which is commonly found in colon and many other cancers.

The scientists also delivered components of the CRISPR system directly into the colon wall to quickly model colon cancer by editing the APC gene. They then added CRISPR components to also edit the gene for P53, which is commonly mutated in colon and other cancers.

"These new approaches reduce the time frame to develop genetically engineered mice from two years to just a few months, and involve very basic gene engineering with CRISPR," Roper says. "We used P53 and KRAS to demonstrate the principle that the CRISPR editing approach and the organoid transplantation approach can be used to very quickly model any possible cancer-associated gene."

In this study, the researchers also showed that they could grow tumor cells from patients into organoids that could be transplanted into mice. This could give doctors a way to perform "personalized medicine" in which they test various treatment options against a patient's own tumor cells.

Yilmaz' lab is now using these techniques to study how other factors such as metabolism, diet, and aging affect colon cancer development. The researchers are also using this approach to test potential new colon cancer drugs.

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New model could speed up colon cancer research: Introducing ... - Science Daily

Research at the University of Illinois at Urbana-Champaign has provided the first evidence that viruses and hosts share highly similar regulatory sequences in their promoters -- the initiation sequences of human genes that code for functional proteins.

"To date viral-host networks include protein and mRNA interactions between viruses and their hosts at later stages of gene expression, but our discovery of genetically coupled promoters is novel. They present an additional layer of regulatory synchrony between virus and host, established and poised before either expresses their protein products," explained Roy Dar, an assistant professor of bioengineering at Illinois.

Latent or dormant HIV infected cell reservoirs have been identified as the major barrier towards a cure due to their ability to spontaneously reactivate after removal of antiretroviral therapy. Leading strategies for eradication of HIV attempt to reactivate the whole latent reservoir and clear it with current drug cocktails, a process referred to as 'shock and kill' therapy.

"Promoters of genes coded within our DNA and the HIV-1 viral promoter which initiates active replication of the virus are strongly coupled in their regulation leading to co-expression -- potentially for a viral fitness advantage. In this study, we investigated a specific T-cell migratory pathway that HIV has coupled to, gaining therapeutic insights currently unknown to the HIV cure research community," Dar added.

Promoter similarity of human immunodeficiency virus (HIV) and a human surface receptor allows shared activators to co-regulate viral-host gene expression (blue and red in the cell nucleus). Viral proteins bind cell surface receptors enabling viral control of host cell migration (right side). Those same viral proteins form viral offspring which are shed from the host cell and increase infectious risk to the moving cell's environment.

Promoter similarity of human immunodeficiency virus (HIV) and a human surface receptor allows shared activators to co-regulate viral-host gene expression (blue and red in the cell nucleus). Viral proteins bind cell surface receptors enabling viral control of host cell migration (right side). Those same viral proteins form viral offspring which are shed from the host cell and increase infectious risk to the moving cell's environment.

Within the systems and synthetic biology fields, the group's findings reveal an additional layer of regulation with which viruses co-evolve with coding-genes and interlace pathways in their hosts.

"The study also presents a mechanism for synchronizing initiation of gene expression in synthetic gene circuitry," stated Kathrin Bohn-Wippert, a postdoctoral researcher and first author of the paper, "Genetic coupling of viral-host gene expression presents migratory challenges in HIV therapies" (10.1038/NCOMMS15006), appearing in Nature Communications. "Specifically, in this framework of viral-host genetic coupling we found that the HIV and human CXCR4 promoters are co-regulated and co-expressed. CXCR4 is a chemokine receptor involved in one of the major migratory pathways throughout our body."

"We have demonstrated, for the first time, that the virus co-expresses with the receptor in order to control infected cell migration and its importance in HIV 'shock and kill' eradication strategies (therapies towards a cure). We also demonstrated how drug treatments can differentially control infected cell migration and/or reactivation of the virus from its latent and inactive state," she said.

According to the researchers, additional network mapping of the coevolution of virus and host-cell gene regulatory coupling will guide future therapeutic strategies, expand systems biology efforts on viral-host networks, and provide novel design principles to reverse bioengineer viral circuitry for synthetic biology and gene therapies.

"For the HIV Cure Community we hope this study will raise awareness to the added challenges facing leading strategies towards a cure," remarked Dar, who is also affiliated with the Carl R. Woese Institute for Genomic Biology and the Center for Biophysics and Quantitative Biology at Illinois. "We hope this study will provide new insights to exploit viral-host relationships and viral control of cell migration for advanced therapeutic strategies."

Co-authors include Melina Megaridis and Erin Tevonian, both bioengineering undergraduate researchers, in the Illinois Cancer Scholars Program, and in the Dar "Noise Biology" Lab.

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Insights to redirect leading HIV cure strategy - Science Daily

Schulman IRBhas launched a new service to ensure sponsors, CROs, and others are compliant when conducting genetic engineering research given the diverse risks, says committee lead.

The institutional biosafety committee (IBC) service will be headed by Dr. Daniel Eisenman, Ph.D., RBP, SM(NRCM), CBSP, who told us the service provides a means of obtaining regulatory approvals to perform gene therapy research and research involving genetic engineering.

The field of gene therapy is no longer science fiction as the US, Europe, and China have started approving genetically modified therapeutics in recent years, Eisenman added.

Technological advances have created a wealth of potential genetically modified therapeutics that are either ready or on the verge of being ready for clinical trials, and many clients have been asking us to provide a commercial IBC service.

As Eisenman explained, IBC review often comes as a surprise to clinical researchers not familiar with gene therapy research requirements though IBC review shouldnt be an obstacle to conducting innovative research, he said.

Eisenman explained NIH guidelines require approval from both an IBC and an IRB given the diverse risks associated with gene therapy research. As such, Schulman will offer its IBC services as well as central IRB services for a coordinated review process.

Rather than having to wait for one committees approval before the other review can begin, conducting the reviews concurrently means the committees work together collaboratively, which accelerates the regulatory approval process, said Eisenman.

The new IBC service offers complete setup, registration support, and administrative resources for sites to operate an NIH-compliant IBC.

The service will support clinical, pre-clinical and non-clinical research, providing all components to complement an existing IBC or build and administer an entirely new IBC from the ground up, Eisenman added.

After conducting a risk assessment, the committee focuses on the associated containment and safety practices while looking at occupational safety as well as the protection of the community and environment surrounding the research site to ensure a comprehensive risk mitigation plan is in place.

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Gene therapy no longer science fiction: IRB launches biosafety committee service - OutSourcing-Pharma.com

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Dimension Therapeutics Inc (DMTX) Upgraded at Zacks Investment Research Markets Daily According to Zacks, Dimension Therapeutics, Inc. is a biotechnology company which focuses on developing novel, liver-directed gene therapy treatments for severe, rare genetic disorders. The company's pipeline of programs includes DTX101, a lead gene ... Dimension Therapeutics (DMTX) Earning Favorable News Coverage, Report ShowsSports Perspectives all 4 news articles »

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Dimension Therapeutics Inc (DMTX) Upgraded at Zacks Investment Research - Markets Daily

Be The Match BioTherapies announces collaboration agreement with Magenta Therapeutics.

MINNEAPOLIS, May 2, 2017 Be The Match BioTherapiesSM, an organization offering solutions for delivering autologous and allogeneic cellular therapies, today announced that it has entered into a strategic partnership with Magenta Therapeutics, a biotechnology company developing therapies to improve and expand the use of curative stem cell transplantation. The collaboration is intended to support efforts to improve transplant outcomes and expand the application of stem cell transplantation into disease indications that include autoimmunity, serious inherited immune and metabolic disorders, blood defects and blood cancers. Be The Match BioTherapies also announced today that it is participating in Magentas Series B financing round, its first equity investment as an organization.

Under the terms of the collaboration agreement, Be The Match BioTherapies and Magenta will explore opportunities to work together across Magentas discovery, clinical development and product delivery efforts. The collaboration leverages a wide range of Be The Match BioTherapies research assets and services, including the National Marrow Donor Program(NMDP)/Be The Match marrow registry, the largest in the world with nearly 16 million volunteer marrow donors. Magenta may also collaborate with Be The Match BioTherapies in the design of clinical trials and of its cell therapy delivery platform and services.

Partnering with Magenta in its efforts to revolutionize the current state of stem cell transplantation aligns with our core mission to help organizations deliver cellular therapies that save more lives and improve the quality of life for patients, said Amy Ronneberg, President of Be The Match BioTherapies. Our collaboration with Magenta exemplifies how cell and gene therapy companies can benefit from our robust network of products and services regardless of where they are in the development life cycle. We look forward to lending our expertise in cellular therapy and leveraging our deep-rooted relationships, partnerships and global infrastructure to support the development of powerful treatment options with great potential to improve patient outcomes in a range of disease areas.

Jason Gardner, D. Phil., Chief Executive Officer, President, and Cofounder of Magenta, added: We believe that Be The Match BioTherapies extensive experience and network in stem cell transplant medicine, coupled with Magentas work in patient conditioning and stem cell harvesting and growth, could accelerate our development path and ability to positively impact patients lives.

Be The Match BioTherapies launched in 2016 as a subsidiary of NMDP/Be The Match, the national organization with a 30-year history of connecting patients with their donor match for a life-saving bone marrow or umbilical cord blood transplant. As experts in providing services and expertise to organizations pursuing life-saving treatments in the cellular therapy space, Be The Match BioTherapies aims to help critically ill patients who can benefit from these treatments.

(Source:Business Wire)

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Cell Therapy Company Joins Forces with Biotech in New Transplantation Research Alliance - Pharmaceutical Processing

Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

The findings are published in the April 21 advance online issue ofCell Research.

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes' photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene calledNrland a downstream transcription factor calledNr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating eitherNrlorNr2e3reprogrammed rod cells to become cone cells.

"Cone cells are less vulnerable to the genetic mutations that cause RP," said Zhang. "Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision."

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. "AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile," said Zhang. "Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer."

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Using CRISPR to Reverse Retinitis Pigmentosa, Restore Visual Function - Drug Discovery & Development

-- Investor breakfast event and webcast at ASGCT on Friday, May 12 at 7:00 a.m. EDT --

LEXINGTON, Mass. and AMSTERDAM, the Netherlands, May 01, 2017 (GLOBE NEWSWIRE) -- uniQure N.V. (QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced company presentations at the following conferences taking place in May:

American Society of Gene and Cell Therapy (ASGCT), May 10 13 2017, at the Marriott Wardman Park hotel in Washington, D.C.

UBS Global Healthcare Conference, May 22 24 2017, at the Grand Hyatt New York, in New York City.

American Biomanufacturing Summit, May 23 24 2017, at the Hyatt Regency Mission Bay Spa & Marina, in San Diego, California.

About uniQure uniQure is delivering on the promise of gene therapy single treatments with potentially curative results. We are leveraging our modular and validated technology platform to rapidly advance a pipeline of proprietary and partnered gene therapies to treat patients with hemophilia, Huntingtons disease and cardiovascular diseases. http://www.uniQure.com.

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uniQure Announces Company Presentations at Upcoming May Conferences - Yahoo Finance

Analyst Activity BTIG Research Reiterates Buy on bluebird bio (NASDAQ:BLUE) Market Exclusive With its lentiviral-based gene therapy and gene editing capabilities, it has built an integrated product platform with various applications in these areas. The Company's clinical programs in severe genetic diseases include its LentiGlobin product ... and more »

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Analyst Activity BTIG Research Reiterates Buy on bluebird bio (NASDAQ:BLUE) - Market Exclusive

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Regenxbio Inc (RGNX) Stock Rating Upgraded by Zacks Investment Research The Cerbat Gem The Company focuses on the development, commercialization and licensing of recombinant adeno-associated virus gene therapy. Its products candidates include RGX-501, for the treatment of homozygous familial hypercholesterolemia which uses the AAV8 ... Vittal Vasista Sells 3100 Shares of Regenxbio Inc (RGNX) StockTranscript Daily all 14 news articles »

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Regenxbio Inc (RGNX) Stock Rating Upgraded by Zacks Investment Research - The Cerbat Gem

Can a childhood cancer doctor like me have insights about that other end of medicine older adults with dementia? A baby acutely ill with leukemia seems like the polar opposite of a woman with Alzheimer's disease (AD), with her slow, insidious deterioration. Yet each can be progressive and fatal. I've cared for both, in different ways.

As a husband and caregiver, confronting my wife's Alzheimer's disease, I am appalled by the lack of effective therapy for her. As a clinical investigator, I'm appalled by what I see as a lack of direction in clinical dementia research, a lack of structure and a lack of ambitious leadership.

"Every Minute Counts," the PBS TV documentary that aired recently, showed the heart-rending personal devastation of Alzheimer's disease and dementia, and the enormous cost of care for those affected. It ended with a plea for more funding and research. But after decades of research and billions already spent, why aren't we further?

Alzheimer's is now the sixth leading cause of death in the U.S.; it was only 13th two decades ago. Many AD experts acknowledge the lack of progress. Last year, two researchers even wrote that seeking an AD cure is a notion "many believe unrealistic," and that advocating for curative therapy "verges on the promotion of false hope."

Since my wife was diagnosed, just one new drug really a combination of two older drugs has been approved for Alzheimer's. As a cancer doctor, I've watched more than 70 cancer treatments get approved during those same five years.

Even the Alzheimer's Association plainly states "there is no cure for Alzheimer's." Not so plainly stated is that we don't know what causes it, how it happens or how to prevent it.

Of course, we don't really know what causes childhood leukemia either, how it happens or how to prevent it, even with our current sophisticated molecular descriptions and theories. But the survival rate for the most common childhood leukemia has gone from less than 10 percent in the 1960s to over 90 percent now, with incremental progress every five years. Most kids are cured with combination chemotherapy that was developed decades ago, before molecular testing.

Most AD funding goes for molecular or non-therapeutic research, at the expense of clinical work. Sickle cell anemia was called the first "molecular disease" over 60 years ago; we still don't have a cure, even though just this year we might have a gene therapy for it. In AD, the molecular genetics seems more complicated. AD patients have waited years for any therapy, much less one from "precision medicine." Is this the right strategy?

It's not all bad news. Last year, three commercial drug trials announced results, and they showed glimmers of hope. Two were reported as failures by the media, but company press releases (TauRx, Lilly) reported modest positive effects. The third drug, from Biogen, seemed better at slowing the decline in some patients, but it evidently did not stop the disease.

AIDS therapy, like cancer, is an area of medicine that seemed hopeless at first. The leadership of Dr. William Paul, an "AIDS Czar," is credited with accelerating clinical progress in that condition. Still incurable, nevertheless AIDS patients' lives are now extended from months to years.

Nothing has really changed for Alzheimer's patients over the past five years. Brilliant scientists are working, but in the usual atmosphere of creative academic chaos. There are a few AD clinical trial groups, much like cancer trials groups, but the comparison of their activity is stark. In the state of Washington, where I live, there are over 600 cancer studies recruiting patients; in AD there are about a dozen such studies.

Much foundational AD work still needs to be done at the bedside, in overall strategy, trial coordination, informed consents, vigorous subject recruitment and consensus development, so appointing an accountable, identifiable, directive clinical research leader seems like an important way to accelerate progress.

Dr. Ron Louie is a clinical professor of pediatrics at the University of Washington, Seattle; his email is ronlouie@u.washington.edu.

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Alzheimer's clinical research lacks leadership - Baltimore Sun

Women at the highest genetic risk for bone fractures benefit the most from hormone therapy, according to a University at Buffalo study of 10,000 participants in the national Women's Health Initiative.

As women age, their bone mineral density decreases, leaving them at greater risk of breaking bones from falls. Some women are more genetically prone to fractures. The researchers said their study is believed to be the first to investigate gene-hormone therapy interaction on fractures in postmenopausal white women.

We found that women who are genetically at the highest fracture risk can enjoy the greatest protection from fracture when they use hormone therapy, Heather Ochs-Balcom, a UB associate professor of epidemiology and environmental health who led the research team, said in a statement.

The findings were published online in the Journal of Clinical Endocrinology and Metabolism. The papers first author, Youjin Wang, conducted the research as a doctoral candidate in epidemiology and environmental health at UB.

Researchers looked at a subset of 9,922 women among the more than 27,000 who had participated in Women's Health Initiative hormone therapy clinical trials. The federally funded Initiative began in 1991 and consisted of a set of studies looking at health issues in more than 161,000 postmenopausal women.

Further studies on gene-therapy interaction are needed to evaluate the advantages of targeted treatments based on genetic profile, the researchers said.

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UB study suggests reduced fracture risk with hormone therapy in ... - Buffalo News

"Sangamo once again has a very strong presence at ASGCT, with 19 oral and poster presentations," said Dr. Sandy Macrae, Sangamo's chief executive officer. "These data highlight the breadth of our clinical and early stage pipeline across genome editing, gene therapy, gene regulation and cell therapy. With our focus now on the translation of our groundbreaking science into new genomic therapies that transform patients' lives, our research and technology programs will continue to provide new assets for therapeutic development."

The following presentations are scheduled at the ASGCT Meeting sessions:

Invited Presentations at Scientific Symposia

Lysosomal Storage Disorders

Central Nervous System Disorders

Monogenic and Infectious Diseases

Technology and Delivery Developments

Applications of Gene Editing in Stem Cells

All abstracts for the ASGCT meeting are available online at 2017 ASGCT Annual Meeting Abstracts.

About Sangamo Therapeutics Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic therapies that transform patients' lives using the company's industry leading platform technologies in genome editing, gene therapy, gene regulation and cell therapy. The Company is advancing Phase 1/2 clinical programs in hemophilia A and hemophilia B, and lysosomal storage disorders MPS I and MPS II. Sangamo has a strategic collaboration with Bioverativ Inc. for hemoglobinopathies, including beta thalassemia and sickle cell disease, and with Shire International GmbH to develop therapeutics for Huntington's disease. In addition, it has established strategic partnerships with companies in non-therapeutic applications of its technology, including Sigma-Aldrich Corporation and Dow AgroSciences. For more information about Sangamo, visit the Company's website at http://www.sangamo.com.

Forward Looking StatementsThis press release contains forward-looking statements based on Sangamo's current expectations. These forward-looking statements include, without limitation, references relating to presentation of data from various therapeutic and research programs and the potential of these programs to transform the lives of patients. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the dependence on the success of clinical trials of lead programs, the lengthy and uncertain regulatory approval process, uncertainties related to the timing of initiation and completion of clinical trials, whether clinical trial results will validate and support the safety and efficacy of ZFP Therapeutics, and the ability to establish strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable gene-based therapeutics. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Reports on Form 10-K and Quarterly Reports on Form 10-Q as filed with the Securities and Exchange Commission. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Therapeutics Announces Presentations at 2017 Annual meeting of the American Society of Gene & Cell ... - PR Newswire (press release)

Confocal micrograph of mouse retina depicting optic fiber layer. Image courtesy of National Center for Microscopy and Imaging Research, UC San Diego.

Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

The findings are published in the April 21 advance online issue of Cell Research.

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.

Cone cells are less vulnerable to the genetic mutations that cause RP, said Zhang. Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile, said Zhang. Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.

This article has been republished frommaterialsprovided by University of California - San Diego. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference

Zhu, J., Ming, C., Fu, X., Duan, Y., Hoang, D. A., Rutgard, J., . . . Zhang, K. (2017). Gene and mutation independent therapy via CRISPR-Cas9 mediated cellular reprogramming in rod photoreceptors. Cell Research. doi:10.1038/cr.2017.57

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Reversing Gene Damage to Treat Blindness | Technology Networks - Technology Networks

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Using CRISPR to reverse retinitis pigmentosa and restore visual ... Science Daily Using the gene-editing tool CRISPR/Cas9, researchers have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing ... and more »

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Using CRISPR to reverse retinitis pigmentosa and restore visual ... - Science Daily

BUFFALO, N.Y. Women at the highest genetic risk for fracture benefit the most from hormone therapy, according to a first-of-its-kind study led by researchers at the University at Buffalo.

The study included nearly 10,000 participants from the Womens Health Initiative (WHI), a national, long-term study of more than 150,000 women.

We found that women who are genetically at the highest fracture risk can enjoy the greatest protection from fracture when they use hormone therapy, said Heather Ochs-Balcom, associate professor of epidemiology and environmental health in UBs School of Public Health and Health Professions, who led the research team.

The findings were published online ahead of print in the Journal of Clinical Endocrinology and Metabolism. The papers first author, Youjin Wang, conducted the research as a doctoral candidate in epidemiology and environmental health at UB.

This study provides a better understanding of who can benefit the most in terms of bone health from hormone therapy use, Ochs-Balcom said, adding that the results have implications for personalized medicine. Its important information as women and their doctors make decisions about hormone therapy use.

The study, believed to be the first to investigate gene-hormone therapy interaction on fracture in postmenopausal white women, utilizes the largest set of known genes linked to fracture risk from a meta-analysis of genome-wide association studies.

Researchers looked at a subset of 9,922 women from among the more than 27,000 who had participated in WHI hormone therapy clinical trials. They wondered whether women who are more genetically susceptible to fractures could benefit from hormone therapy.

This is important because, as previous WHI studies have identified, there are risks and benefits with hormone therapy, Ochs-Balcom said. This is where precision or personalized medicine comes in the attempt to get the right drugs to the right person to ensure the most benefit and least harm.

As women age, their bone mineral density (BMD) decreases, leaving them at greater risk of breaking bones from falling, which also increases as they age. But some women also are more genetically prone to fractures. Our study represents a first look at how inherited predisposition to fracture is related to hormone therapy use, said Ochs-Balcom, who also holds a faculty appointment in the program in Genetics, Genomics and Bioinformatics in UBs Jacobs School of Medicine and Biomedical Sciences.

Wang notes that further studies on gene-therapy interaction are warranted to evaluate the advantages of targeted interventions based on genetic profile. The research team is currently analyzing other gene-environment interactions and recently published another paper on the association of calcium plus vitamin D supplementation and genetic risk of fracture.

In addition to Wang and Ochs-Balcom, other UB co-authors include Jean Wactawski-Wende, dean of the School of Public Health and Health Professions and SUNY Distinguished Professor and professor of epidemiology and environmental health; and Leah Preus, Kathleen Hovey and Jing Nie from the School of Public Health and Health Professions.

Additional co-authors include Lara Sucheston-Campbell, Rebecca Jackson and Samuel Handelman, The Ohio State University; Rami Nassir, University of California, Davis; and Carolyn Crandall, University of California, Los Angeles.

The Womens Health Initiative began in 1991 and consisted of a set of clinical trials and an observational study. Combined, they included more than 161,000 generally healthy postmenopausal women aged 50 to 79.

One of 40 WHI centers nationwide, the University at Buffalo serves as the Northeast Regional Center, managing data collection and scientific coordination among nine WHI-affiliated institutions in the mid-Atlantic and Northeast regions. UB has received WHI extension funding to conduct follow-up studies on the original participants, many of whom are now between ages 67 and 100.

The WHI is funded by the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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Genetics are key to hormone therapy lowering risk of broken bones in older women - UB News Center

Underlying cause of a form of macular degeneration characterized Science Daily The new information sets the team up for testing a gene therapy to treat the disease, as the researchers will be able to observe whether or not these structural and biochemical abnormalities have been corrected. "Now that we understand what we're ...

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Underlying cause of a form of macular degeneration characterized - Science Daily

Newswise Using the gene-editing tool CRISPR/Cas9, researchers at University of California San Diego School of Medicine and Shiley Eye Institute at UC San Diego Health, with colleagues in China, have reprogrammed mutated rod photoreceptors to become functioning cone photoreceptors, reversing cellular degeneration and restoring visual function in two mouse models of retinitis pigmentosa.

The findings are published in the April 21 advance online issue of Cell Research.

Retinitis pigmentosa (RP) is a group of inherited vision disorders caused by numerous mutations in more than 60 genes. The mutations affect the eyes photoreceptors, specialized cells in the retina that sense and convert light images into electrical signals sent to the brain. There are two types: rod cells that function for night vision and peripheral vision, and cone cells that provide central vision (visual acuity) and discern color. The human retina typically contains 120 million rod cells and 6 million cone cells.

In RP, which affects approximately 100,000 Americans and 1 in 4,000 persons worldwide, rod-specific genetic mutations cause rod photoreceptor cells to dysfunction and degenerate over time. Initial symptoms are loss of peripheral and night vision, followed by diminished visual acuity and color perception as cone cells also begin to fail and die. There is no treatment for RP. The eventual result may be legal blindness.

In their published research, a team led by senior author Kang Zhang, MD, PhD, chief of ophthalmic genetics, founding director of the Institute for Genomic Medicine and co-director of biomaterials and tissue engineering at the Institute of Engineering in Medicine, both at UC San Diego School of Medicine, used CRISPR/Cas9 to deactivate a master switch gene called Nrl and a downstream transcription factor called Nr2e3.

CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, allows researchers to target specific stretches of genetic code and edit DNA at precise locations, modifying select gene functions. Deactivating either Nrl or Nr2e3 reprogrammed rod cells to become cone cells.

Cone cells are less vulnerable to the genetic mutations that cause RP, said Zhang. Our strategy was to use gene therapy to make the underlying mutations irrelevant, resulting in the preservation of tissue and vision.

The scientists tested their approach in two different mouse models of RP. In both cases, they found an abundance of reprogrammed cone cells and preserved cellular architecture in the retinas. Electroretinography testing of rod and cone receptors in live mice show improved function.

Zhang said a recent independent study led by Zhijian Wu, PhD, at National Eye Institute, part of the National Institutes of Health, also reached similar conclusions.

The researchers used adeno-associated virus (AAV) to perform the gene therapy, which they said should help advance their work to human clinical trials quicker. AAV is a common cold virus and has been used in many successful gene therapy treatments with a relatively good safely profile, said Zhang. Human clinical trials could be planned soon after completion of preclinical study. There is no treatment for RP so the need is great and pressing. In addition, our approach of reprogramming mutation-sensitive cells to mutation-resistant cells may have broader application to other human diseases, including cancer.

Co-authors include: Jie Zhu and Xin Fu, Guangzhou Women and Childrens Medical Center; Chang Ming, Duc Ahn Hoang and Wenjun Xiong, City University of Hong Kong; Yaou Duan, Jeffrey Rutgard, Runze Zhang, Wenqui Wang, Daniel Zhang, Edward Zhang and Charlotte Zhang, Shiley Eye Institute, Institute for Engineering in Medicine and Institute for Genomic Medicine, UC San Diego; Rui Hou, Guangzhou KangRui Biological Pharmaceutical Technology Company; Xiaoke Hao, Fourth Military Medical University; and the Eye Gene Therapy Consortium.

Funding for this research came, in part, from the Richard Annesser Fund, the Dick and Carol Hertzberg Fund, the National Basic Research Program of China, Hi-Tech Research and Development Program of China, Hon Kong General Research Fund and Early Career Scheme and Shenzhen Science and Technology Fund.

###

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Using CRISPR to Reverse Retinitis Pigmentosa and Restore Visual ... - Newswise (press release)

Despite reports that linked Novartis to cutting back on its cell therapy work, the Swiss major said it is going full steam ahead for its CAR-T research as a potential approval for its candidate appears on the horizon.

In August of last year,Endpointsbroke the news thatthe Big Pharma was integratingits once standalone gene and cell therapy unit into the company. Most employees would beredeployed, but around 120 potentially face job losses.

This unit was doing work on the next new cancer class CAR-T, but some speculated that the disbanding of this unit meant that Novartis was looking to take a step back from research in this area.

Talk of its death was, however, greatly exaggerated according the the company. It saidits leading CAR-T candidate, CTL019 (tisagenlecleucel), now has two FDA breakthrough tags in two blood cancers, and was given a priority review for the med by the agency at the end of March.

The company is now in a race with biotech Kite Pharma to be the first to market this new type of cancer therapy that has shown some stellar results in clinical trials (although it also has revealedsome serious side effects from other companies, including Juno Therapeutics).

Speaking to FierceBiotech, Vas Narasimhan, M.D., global head of drug development and CMO at Novartis, said that there was a lot of interpretation last year regarding our reintegrating our cell and gene therapy unit into our R&D infrastructure, but was adamant that this did not create any difference in regards to our commitment in this space.

He said the integration of the unit into Novartis proper was primarily due to its success.

We had incubated the technology which came out of [its 2012 CAR-T deal] with Penn as a dedicated unit, and that was something that made sense: If you had immediately put that into the larger infrastructure of Novartis, it would have got lost, especially in the early stages when it was risky and it was unclear if this would be tractable," he said.

But Narasimhan said that as the unit became scaled, the parallel infrastructure scheme no longer made optimal sense.

To give this technology the best chance of succeeding, and in the most cost-effective way, we decided we should integrate [the unit] into our normal operations, and so CAR-T agents were then no different to an I-O agent, or anything else that we developed at Novartis, other than the fact that the process here is very important for the product," he said. We have the scale to work on these sorts of things quickly. So, the integration has allowed us to work on multiple programs in parallel, where I think the unit was focusing on just one or two programs at a time.

Now integrated, Narasimhan said its full steam ahead for CAR-T, and the immediate focus is to see through the two indications: r/r B-cell acute lymphoblastic leukemia (ALL) in pediatric and young adult patients and r/r diffuse large B-cell lymphoma (DLBCL) for tisagenlecleucel this year, as well as a combined ALL and DLCBL submission in Europe in 2017.

On the R&D side, he sees a three-pillar approach for CAR-T. The first pillar is to continue to be innovative on the manufacturing side of things, which is a tricky and cutting-edge science in itself for CAR-T. We need to continue to invest to optimize our manufacturing platforms, bringing it to more patients as we expand indications, he says.

The second is to continue to work in blood cancers, where results for Novartis and others have been the strongest. He said that they have programs in CAR-T in combination with other meds, as well as research in multiple myeloma, with additional blood cancer programs also slated to run on its CAR-T platform.

And the third pillar, which could turn out to be the toughest for all involved, is the move into solid tumors.

We have a few different constructs now and were moving into the clinic, Narasimhan explains. Our most advanced CAR-T is targeting ovarian cancer as well as a few other solid tumors.

Solid tumor research in the industry using CAR-Ts has not to date, however, seen a translation from the strong data coming out of blood cancers, and a lot of uncertainty remains as to whether, and how, CAR-T can treat these types of cancer.

I asked Narasimhan how confident he and Novartis were in holding up its third pillar.

For solid tumors, we really need to wait for the clinical data to make a judgement and see how tractable it is. We know in the solid tumor microenvironment there is a lot more going on, and the question of course will be combination therapies and what kind of I-O combinations might be required to see deep and durable responses in solid tumors," he said."Its too soon to say what our confidence level is in solid tumors, other than to say that we have targets that we are interested in and weve built those constructs and are taking them into the clinic.

One of the big questions surrounding Novartis CAR-T program is the outcome of its JULIET trial for tisagenlecleucel, a study looking at the meds ability in DLCBL (where rival Kite is also working on). The data are in, but Novartis isnt sharing yet.

Our plan with JULIET is to announce it at an upcoming medical event, and once we get acceptance at a congress, well disclose it. We just want to ensure that we dont undermine our ability to present the data to a scientific congress.

But Narasimhan did say that the breakthrough designation it got this week from the FDA hopefully gives some indication, of how the data have panned out.

Lastly, we spoke about the FDA, which is under pressure from all directions as the new administration looks to cut back on regulations and direct funding (with a proposed increase in user fees), and internally, with some questioning whether it has at times lowered its standards to allow drugs through, such as those from Sarepta and more recently Marathon, and if this signals a sea change for the agency.

Narasimhan defended the FDA, saying it should be strong, but that it is under-resourced for what they have to do. If you look at 21st Century Cures Act and all the new things they have to do, the funding isnt necessarily all there yet for those new requirements.

He also saidthat the science and the technology being put up for review is getting more and more complex, and there is public pressure with right to try and patient group pressures as well on the FDA and these are only increasing, so they have to find the right balance."

I would say, in general, that the FDA does an extraordinary job having worked with them for many years, including on the H1N1 pandemic, and through various cycles of innovation. But, I think they need more time and money to invest in their people, so that they are up to speed on the latest science so that they can make measured decisions.

He said that despitethe agency's outlier cases,generally they continue to be very rigorous, in their reviews.

He also said it was incumbent on both the agency and the industry to do more to speed up R&D and approvals, and be open to new, but scientifically-led, approaches that can help get new drugs to patients more quickly.

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Novartis drug development chief outlines CAR-T research commitment - FierceBiotech

NEW YORK (GenomeWeb) Genetic testing for inherited retinal diseases is often not covered routinely by health insurance, yet a molecular diagnosis is required for enrollment in a number of clinical trials for new gene- or mutation-specific treatments. To assess the benefit of genetic testing data and to enable more patients to take advantage of it, the Foundation Fighting Blindness has been conducting a pilot research program, providing gene panel testing to 100 members of its My Retina Tracker patient registry free of charge.

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Inherited Retinal Disease Patients, Therapy Developers May Benefit From New Genetic Testing Program - GenomeWeb

Dr. Nabil Ahmed and Dr. Stephen Gottschalk discuss their investigation of a new treatment option for glioblastoma, the most common brain tumor in humans.

Glioblastoma is the most common brain tumor in humans and also one of the most difficult cancers to treat; patients with this type of cancer only survive about one year from time of diagnosis. Researchers at Baylor College of Medicine, Texas Childrens Cancer Center, and the Center for Cell and Gene Therapy at Baylor, Texas Childrens Hospital and Houston Methodist are investigating a new treatment option using modified T cells with anti-tumor properties with the goal of improving outcomes for patients with glioblastoma.

Their research focuses on engineered T cells that target the protein HER 2 expressed in low levels in glioblastoma cells. Results of a Phase 1 study published in the current issue of JAMA Oncology established the safety of these HER 2-specific, chimeric antigen receptor modified T cells (CAR T cells) when infused in to patients in increasing doses and, importantly, results also showed a clinical benefit to patients.

Our inability to effectively treat glioblastoma has been one of the failures of oncology, said Dr. Nabil Ahmed, associate professor of pediatrics at Baylor, Texas Childrens Cancer Center and the Center for Cell and Gene Therapy and first author of the paper. Glioblastoma is resistant to standard therapy, and it is difficult to remove all of the tumor cells through surgery without damaging the brain, so there is an urgent need for new and better treatment. Our work has focused on immune therapy, because it is very targeted and uses tumor-killing mechanisms that the cancers have not shown resistance to in the lab.

CAR T cells are T cells a type of immune cells involved in the defense against tumors that have been programmed to recognize and kill tumor cells carrying one specific antigen, in this case HER2, on the surface of cancer cells through an artificial molecule, the CAR, expressed on their surface.

The study included 17 pediatric and adult patients with HER 2-positive glioblastoma who received up to five escalating doses of the engineered T cells through intravenous infusions. Establishing the safety of the treatment is important, as other immunotherapy treatment approaches for solid tumors have resulted in significant side effects and toxicities for patients, Ahmed said.

First and foremost, the cells were safe. We did not see any life threatening side effects. Along with this we also saw measurable tumor responses, Ahmed said.

Median survival of patients who participated in the trial was 11.1 months post T cell infusion and 24.5 months from diagnosis. Three patients in the trial experienced no disease progression after more than two years of follow up.

With their promising results, Ahmed and his research colleagues, including Dr. Stephen Gottschalk, professor of pediatrics at Baylor, Texas Childrens Cancer Center and the Center for Cell and Gene Therapy and senior author of the paper, turn their focus to the next steps in the research.

In this phase 1 clinical trial we tested a particular modification that renders these cells specific for HER 2 and while the results have been encouraging, we are very interested to further engineer these cells, for example by making the T cells more effective after the infusion and by targeting not only HER2 but other molecules that are expressed on the cell surface of brain tumors, Gottschalk said.

The CAR T cells are produced in the cell manufacturing facility of the Center for Cell and Gene Therapy. Baylor is one of the few academic institutions that has such a facility, Gottschalk noted.

Others who contributed to this study include Vita Brawley, Meenakshi Hegde, Kevin Bielamowicz, Mamta Kalra, Daniel Landi, Catherine, Robertson, Tara Gray, Oumar Diouf, Amanda Wakefield, Alexia Ghazi, Claudia Gerken, Zhongzhen Yi, Aidin Ashoori, Meng-Fen Wu, Hao Liu, Cliona Rooney, Gianpietro Dotti, Andrea Gee, Jack Su, Yvonne Kew, David Baskin, Yi Jonathan Zhang, Pamela New, Bambi riley, Milica Stojakovic, John Hicks, Suzanne Powell, Malcolm Brenner, Helen Heslop, Roberta Grossman, and Winifred Wels, representing Baylor College of Medicine, Texas Childrens Hospital, Houston Methodist Hospital, and the Institute for Tumor Biology and Experimental Therapy in Frankfurt, Germany.

The study received funding from the Alliance for Cancer Gene Therapy, Cancer Prevention and Research Institute of Texas (RP110553), Alexs Lemonade Stand Pediatric Cancer Foundation, Stand Up to Cancer/St. Baldricks Pediatric Dream Team Translational Research Grant (SU2C-AACR-DT1113), the Clinical Research Center at Texas Childrens Hospital, the Dan L Duncan Institute for Clinical and Translational Research at Baylor, and by shared resources through Dan L Duncan Comprehensive Cancer Center Support Grant from the National Cancer Institute (P30CA125123).

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Clinical trial results show benefit of brain cancer therapy - Baylor College of Medicine News (press release)

April 19, 2017 by Katherine Unger Baillie The Penn-led research team characterized the underlying mechanism that leads to the blinding Best disease; a loss of the microvilli that support and "feed" photoreceptor cells. The contrast can be seen above, with a normal retina on the right and an affected on on the left. Credit: University of Pennsylvania

Named for Friedrich Best, who characterized the disease in 1905, Best disease, also known as vitelliform macular dystrophy, affects children and young adults and can cause severe declines in central vision as patients age. The disease is one in a group of conditions known as bestrophinopathies, all linked to mutations in the BEST1 gene. This gene is expressed in the retinal pigment epithelium, or RPE, a layer of cells that undergirds and nourishes photoreceptor cells, the rods and cones responsible for vision.

Despite the century of work on bestrophinopathies and the identification of genetic mutations responsible for the conditions, no one had identified the underlying mechanism that led to the vision loss seen in Best disease until now.

Using an animal model of Best disease in combination with biochemical and optical assays, a team of researchers at the University of Pennsylvania has pinpointed a number of abnormalities that give rise to the impairments seen in the disease.

"The genetic cause of the disease has been known for 20 years, but no one had samples of patients at the stage when the disease starts," said Karina E. Guziewicz, research assistant professor of ophthalmology in Penn's School of Veterinary Medicine and lead author on the study. But "we were now able to pinpoint this early stage and find out what factors trigger the development of lesions."

The new information sets the team up for testing a gene therapy to treat the disease, as the researchers will be able to observe whether or not these structural and biochemical abnormalities have been corrected.

"Now that we understand what we're seeing, it allows us to judge the success of a particular therapy," said Gustavo D. Aguirre, professor of medical genetics and ophthalmology at Penn Vet.

Kathleen Boesze-Battaglia, a professor in the Department of Biochemistry in Penn's School of Dental Medicine, also contributed her expertise in lipid biochemistry and spectral analysis of lipid debris to the study, which was published in the journal Progress in Retinal and Eye Research, the top ranked journal in the eye-research field.

"Interestingly, the lipid debris accumulation is similar to cholesterol rich plaque formation, compounded by a complexity of vitamin A metabolism," said Boesze-Battaglia. "Alterations in lipid metabolism likely contribute to the secondary disease pathology in this model."

The main puzzle surrounding Best disease was why, despite the BEST1 gene being mutated in the RPE throughout the retina, vision loss struck the macula and fovea, the central areas of the retina responsible for reading and tasks requiring high-resolution vision, while seeming to spare the rest. Researchers had observed lesions in this area, but it was unknown why they developed.

In this study, the Penn-led team discovered that this predilection of the macula to develop lesions has to do with differences in the supporting structures of rods versus cones.

Rods, which make up more than 90 percent of photoreceptor cells in the retina and are responsible for dim-light vision, have a cluster of supporting structures known as RPE microvilli that cup the cell like stakes holding up a plant. In contrast, cones, the color-sensing photoreceptors that make up 3 to 5 percent of all photoreceptors but are overrepresented in the macula, are engulfed in a sheath of microvilli. In addition, cones are supported by an insoluble matrix.

Examining cross-sections of the fovea-like region in the canine macula of dogs affected with the canine equivalent of Best disease, the researchers found that the microvilli don't form and that the matrix is fragmented. The susceptibility of the macula is due to the fact that cones are the predominant cell type there and rely on the matrix for support and nutrient exchange.

"We were not expecting to find such dramatic structural abnormalities," Guziewicz said. "For a hundred years, this has been thought to be a disease of the RPE, but we have now identified this as a disease of the RPE-photoreceptor interface."

"The RPE provides transport of nutrients to the cones and engulfs the discarded part of cones and rods," said Aguirre. "When you lose the matrix, you lose the connection between those cells and the RPE and that leads to disease."

To determine if the same would be true in humans, the researchers looked at human induced pluripotent stem cell-derived RPE from Best disease patients and found similar signatures: microvilli numbers were decreased in length and density. These experiments were conducted in collaboration with David Gamm's laboratory from the McPherson Eye Research Institute at the University of Wisconsin-Madison.

Looking ahead, the research team would like to continue to probe the biochemical signals that lead to the improper development of the microvilli and matrix and push ahead with developing and testing a gene-therapy approach to treating bestrophinopathies.

"Knowing where the disruptions occur will allow us to develop proper outcome measures for a gene therapy, which is in the works," said Guziewicz.

Explore further: Fighting blindness: Scientists bring a key protein into focus

More information: Karina E. Guziewicz et al, Bestrophinopathy: An RPE-photoreceptor interface disease, Progress in Retinal and Eye Research (2017). DOI: 10.1016/j.preteyeres.2017.01.005

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have discovered how a protein called 24 establishes proper vision. Their research helps explain why mutations in the gene encoding 24 lead ...

Newborns babies can be at risk of congenital blindness, presenting sight defects due to lesions or to genetic mutations in their genome. Among the latter, Leber Congenital Amaurosisor LCAis one of the most widespread ...

Silencing a gene called Nrl in mice prevents the loss of cells from degenerative diseases of the retina, according to a new study. The findings could lead to novel therapies for preventing vision loss from human diseases ...

Vitelliform macular dystrophy, also known as Best disease, is one of a group of vision-robbing conditions called bestrophinopathies that affect children and young adults. Caused by inherited mutations in the BEST1 gene, these ...

In humans, a tiny area in the center of the retina called the fovea is critically important to viewing fine details. Densely packed with cone photoreceptor cells, it is used while reading, driving and gazing at objects of ...

Three years ago, a team from the University of Pennsylvania announced that they had cured X-linked retinitis pigmentosa, a blinding retinal disease, in dogs. Now they've shown that they can cure the canine disease over the ...

Named for Friedrich Best, who characterized the disease in 1905, Best disease, also known as vitelliform macular dystrophy, affects children and young adults and can cause severe declines in central vision as patients age. ...

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My decision to get involved with developing gene therapy for neurological disorders came about because my own daughter, Ornella, 11, was born with a rare genetic condition known as Sanfilippo Syndrome, or mucopolysaccharidosis (MPS-IIIA). One in 70,000 babies is born with this life-limiting condition that results from a genetic mutation of a particular enzyme and leads to toxic build-up of heparan sulphate in brain tissue. Heparan sulphate is necessary for the normal function of the brain, but too much can damage tissue.

Heparan sulphate is necessary for the normal function of the brain, but too much can damage tissue.

At present, there is no cure, treatment is palliative and sufferers die in their early teens. Symptoms range from mild developmental delay and hyperactivity, which leads to sleep disturbance to more profound problems, such as paralysis, usually before the child reaches his or her 10th birthday.

Five years ago, Ornella became the first person in the world to have an experimental new drug treatment that we are developing at Lysogene, the biotech company I founded with Olivier Danos, a leading researcher into neurodegenerative disease. He had already been looking into this area of research and was keen to look at novel approaches.

She was part of a Phase 1/2 clinical trial that took place in 2011 and 2012 to gauge the safety of gene therapy using an adeno-associated viral vector known as AAVrH10 to deliver a genetically modified N-sulfoglucosamine sulfohydrolase enzyme directly into the brain cells. This enzyme effectively mops up the excess heparan sulphate and disposes of it. Animal studies had already shown it was safe and effective. The four children involved ranged in age from just under 3 years old to just under seven years old and they were dosed individually, one after the other, over three month intervals. The vector is injected into areas of the brain that show signs of damage during an operation under general anesthesia

AAVrH10 is a viral vector that is able to move into brain cells more efficiently where it delivers the drug. Other AAV vectors have been investigated by other research teams but with less effective uptake of gene therapy in the brain. All AAV vectors are very safe and stable so they are long-lasting. They also seem to cause no harmful effects in brain tissue.

All AAC vectors are very safe and stable so they are long-lasting.

This is a very elegant solution to a problem that is very localised in MPS-IIIA patients. The vector delivers the drug directly to the neurons where it is needed. It is also a once-only therapy because it fixes the faulty DNA of the enzyme permanently. Sadly, many children with genetic diseases need to have regular therapy, which often requires a hospital visit several times a month. This kind of gene therapy should mean that there is no need to repeat it more than once.

Im glad to say that the trial, which only included human patients with advanced disease, was a success and the results were published in Human Gene Therapy in 2014. As well as being safe, the therapy resulted in reduction in symptoms and a big increase in quality of life. Ornella showed tremendous improvement and started sleeping through the night something that had never happened from the day she was born until she was treated at six years old. We are hopeful that the therapy may also have the ability to extend life for patients with this disease. Certainly, this is what we observed in early animal studies. Potentially, it may even be curative.

Without such promising results, there was no way that I could consider continuing with the research programme. If I had not been convinced of its efficacy and safety, I would have called a halt after the initial trials.

We are now preparing to embark on a larger scale Phase 3 clinical trial with 20 patients in all. This will take place in 2018. If all goes well, we hope to market the drug to patients by 2020. I feel really blessed and proud to be involved in such an important project and to part of such a great team at Lysogene.

Karen Aiach is speaking at the RSM Medical Innovations summit on April 22nd. http://www.rsm.ac.uk

Karen Aiach is CEO and founder of Lysogene, a biotech company developing gene therapy for central nervous system disorders.

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Gene therapy for nervous system disorders - The Hippocratic Post - The Hippocratic Post (blog)

Quinnipiac University President John Lahey is the recipient of the Stamford-based Alliance for Cancer Gene Therapys first Edward Netter Award for Business and Industry.

Quinnipiac University President John Lahey is the recipient of the Stamford-based Alliance for Cancer Gene Therapys first Edward Netter Award for Business and Industry.

Quinnipiac president to receive new award from Stamford nonprofit

STAMFORD Outgoing Quinnipiac University President John Lahey ranks at the top of the class for his community service, according to the leaders of one of Stamfords major nonprofits.

The Alliance for Cancer Gene Therapy, which supports the development of cell and gene therapies for cancer, will recognize Lahey on Wednesday at its anniversary gala at the Harvard Club in Manhattan with the first Edward Netter Award for Business and Industry.

ACGT officials said Lahey, an ACGT board member since 2004, embodies the qualities valued by the late ACGT co-founder Edward Netter: intellect, creativity, tenacity, curiosity and compassion.

Im deeply honored to receive the first-ever Edward Netter Award for Business and Industry, Lahey said. Edward was a true visionary. He and his wife Barbara have made such an impact in this area of research. Im delighted that Ive been able to be a part of ACGT and help see their vision of successfully treating cancer advance so quickly.

ACGT co-founder and honorary chairman Barbara Netter will present the award to Lahey.

Im so thrilled to honor Dr. John Lahey, Netter said in a statement. He has worked closely with Edward and me over the years to guide ACGT and to fund some of the most innovative and breakthrough cancer research in decades. I know Edward would be extremely proud to know what ACGT has been able to accomplish these years under the stewardship of John Lahey.

Lahey is the eighth president of Quinnipiac. After arriving at the Hamden institution in 1987, Lahey started a planning process that resulted in the growth of student enrollment from 2,000 to nearly 10,000. He also expanded Quinnipiac from a college to a university, which offers more than 100 programs in its nine schools and colleges.

Last week, he announced his intention to retire next year.

Among the other gala speakers, ACGT research fellow Dr. Robert Vonderheide, of the University of Pennsylvania will discuss breakthroughs using immunotherapy for the treatment of solid cancers. Doug Olson will talk about his experience as one of the first three patients treated in the cancer immunotherapy CAR-T clinical trial developed by ACGT research fellow and Scientific Advisory Council member Dr. Carl June.

Since its founding in 2001, ACGT has provided nearly $27 million in funding for cancer cell, gene and immunotherapy research in North America. ACGT officials said the nonprofit has supported the underlying science that has led to the founding of four companies in the final stages of bringing new treatments to patients: Novartis, Ziopharm, Juno Therapeutics and Turnstone Biologics.

pschott@scni.com; 203-964-2236; twitter: @paulschott

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