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Archive for the ‘Gene Therapy Research’ Category

First gene therapy on the cusp of FDA approval – Pharmacy Today, American Pharmacists Association,

An FDA advisory panel will make the call July 12 to recommend for or against agency approval of the first gene therapy. A favorable decision could see the regulator sanction the treatment by early this fall. Drug manufacturer Novartis and the University of Pennsylvania doctors and scientists who tested it are holding out hope for CAR T-cell therapy, which uses patients’ own genetically modified immune cells to fight blood cancers. In a multinational trial of pediatric patients, it achieved remission in 83% of participants67% of whom remained in remission 1 year later. While CAR T-cell therapy initially would be offered to children and young adults not responding to standard leukemia treatment, research has shown it to be effective in adults as well. Substantial concerns about safety and cost, however, could sway the FDA committee away from approval. Analysts’ projections put the price for a one-time infusion at $300,000$600,000, and there also is the risk of serious adverse effectsincluding neurotoxicity and cytokine release syndrome. Novartis is addressing the safety issue by planning a contained launch of the product, rather than simply unleashing it on the entire market. Under its plan, only 3035 medical centers would be authorized to administer CAR T-cell therapy, most having participated in the clinical trial and all having received extensive training.

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First gene therapy on the cusp of FDA approval – Pharmacy Today, American Pharmacists Association,

Breathing in a New Gene Therapy to Treat Pulmonary Hypertension – Newswise (press release)

Breathing in a New Gene Therapy to treat Pulmonary Hypertension

Newswise (New York, NY July 12, 2017) Mount Sinai has partnered with Theragene Pharmaceuticals, Inc. to advance a novel airway-delivered gene therapy for treating pulmonary hypertension (PH), a form of high blood pressure in blood vessels in the lungs that is linked to heart failure. If the therapy succeeds in human clinical trials, it will provide patients for the first time with a way to reverse the damage caused by PH.

This gene therapy technique comes from the research of Roger J. Hajjar, MD, Professor of Medicine and Director of the Cardiovascular Research Center at the Icahn School of Medicine at Mount Sinai, and has been proven effective in rodent and pig animal models. PH is a deadly disease that disproportionately affects young adults and women; 58 percent of cases are found in young adults and 72 percent are women. There is currently no effective cure for PH, and about 50 percent of people who are diagnosed will die from the disease within five years.

PH is a rare (15-50 cases per million people), rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. The high pressure is caused by abnormal remodeling of the lung blood vessels, characterized by a proliferation of smooth muscle cells and a thickening and narrowing of these vessels, and can lead to failure of the right ventricle of the heart and premature death. Abnormalities in calcium cycling within the vascular cells play a key role in the pathophysiology of pulmonary hypertension, along with deficiencies in the sarcoplasmic reticulum calcium ATPase pump (SERCA2a) protein which regulates intracellular calcium within these vascular cells and prevents them from proliferating within the vessel wall. Downregulation of SERCA2a leads to the proliferative remodeling of the vasculature. This gene therapy, delivered via an inhaled aerosolized spray, aims to increase the expression of SERCA2a protein, and has been shown in rodents and pigs to improve heart and lung function, as well as reduce and even reverse cellular changes caused by PH.

This is a devastating disease, and our work in collaboration with many laboratories across the country has allowed us to identify a specific molecular target and use gene therapy to improve cardiovascular and lung parameters in experimental models of PH. We look forward to starting first-in-human studies using this approach in affected patients, said Dr. Hajjar, the senior author of the studies, highlighting that clinical trials will be underway in the next two years.It may take several years before a product is commercially available for PH patients.

We are excited about the potential for SERCA2a gene therapy as a new modality in treating this serious disease, said Jon Berglin, Chief Executive Officer of Theragene Pharmaceuticals, Inc. We look forward to develop and advance this promising product into the clinic.

This represents another critical advancement in a potentially transformative therapeutic breakthrough by Mount Sinai scientists, demonstrating our commitment to improving health outcomes. We are thrilled to be working with Theragene Pharmaceuticals, and continue to strengthen our expertise in partnering health care innovations with industry, said Erik Lium, PhD, Senior Vice President of Mount Sinai Innovation Partners, the commercialization arm of the Icahn School of Medicine at Mount Sinai.

About Mount Sinai Innovation Partners (MSIP)MSIP is responsible for driving the real-world application and commercialization of Mount Sinai discoveries and the development of research partnerships with industry. The aim is to translate these innovations into healthcare products and services that benefit patients and society. MSIP is responsible for the full spectrum of commercialization activities required to bring the Icahn School of Medicine and the Mount Sinai Health Systems inventions to life. These activities include evaluating, patenting, marketing and licensing new technologies, engaging commercial and non-profit relationships for sponsored research, material transfer and confidentiality, as well as fostering an ecosystem of entrepreneurship within our research and health system communities. For more information, visit

About Theragene Pharmaceuticals, Inc.Theragene is a biopharmaceutical company developing cutting-edge science for the treatment of debilitating diseases. The Companys diverse portfolio consists of preclinical and clinical oncology and cardiology platforms utilizing next generation gene therapy and immunotherapy methods.

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Breathing in a New Gene Therapy to Treat Pulmonary Hypertension – Newswise (press release)

Breakthrough Nanorod Tech Could Deliver Gene Therapy Directly to … – Technology Networks

A new method efficiently transfers genes into cells, then activates them with light. This could lead to gene therapies for cancers

Mineko Kengaku, Tatsuya Murakami, and their colleagues from Kyoto Universitys Institute for Integrated Cell-Material Sciences (iCeMS) have developed a new method that modifies the surface of nanorods, making them more efficient in transporting cancer-killing genes into cells.

The method involves coating gold nanorods, which produce heat when exposed to a near-infrared laser, with the lipids oleate and DOTAP. The lipids enhance the nanorods’ ability to interact with and penetrate cells.

The team also developed a gene carrier, known as a plasmid vector, which includes a heat shock protein that is activated in response to heat.

First, the vector was bound to the enhanced green fluorescent protein (EGFP) gene, and then transferred into mammalian cells by the lipid-coated gold nanorods. Exposing cells to near-infrared laser for ten seconds heated up the gold nanorods, turning on the EGFP gene. Surrounding, non-targeted cells showed little to no EGFP expression.

A protein called TRAIL was then added to the plasmid vector. TRAIL induces cell death in cancer cell lines. Infrared illumination of cells transfected by TRAIL-carrying nanorods led to a high cell death rate in surrounding cancer cells.

The lipid-coated gold nanorods could potentially help with molecular cancer therapies.

This new system provides a unique opportunity for site-directed, light-inducible transgene expression in mammalian cells by a near-infrared laser, with minimal phototoxicity, conclude the researchers in their study published in the journal Scientific Reports.

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


Nakatsuji, H., Kawabata, G. K., Kurisu, J., Imahori, H., Murakami, T., & Kengaku, M. (2017). Surface chemistry for cytosolic gene delivery and photothermal transgene expression by gold nanorods. Scientific reports, 7(1), 4694.

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Breakthrough Nanorod Tech Could Deliver Gene Therapy Directly to … – Technology Networks

First gene therapy ‘a true living drug’ on the cusp of FDA approval – Washington Post

PHILADELPHIA When doctors saw the report on Bill Ludwigs bone-marrow biopsy, they thought it was a mistake and ordered the test repeated. But the results came back the same: His lethal leukemia had been wiped out by an experimental treatment never used in humans.

We were hoping for a little improvement, remembers the 72-year-old retired New Jersey corrections officer, who had battled the disease for a decade. He and his oncologist both broke down when she delivered the good news in 2010. Nobody was hoping for zero cancer.

The pioneering therapy with Ludwig and a few other adults at the University of Pennsylvania hospital paved the way for clinical trials with children. Six-year-old Emily Whitehead, who was near death, became the first pediatric recipient in 2012. Like Ludwig, she remains cancer-free.

Such results are why the treatment is on track to become the first gene therapy approved by the Food and Drug Administration. An FDA advisory committee will decide Wednesday whether to recommend approval of the approach, which uses patients own genetically altered immune cells to fight blood cancers.

If the panel gives the nod, the agency probably will follow suit by the end of September. That would open the latest chapter in immunotherapy a true living drug, says Penn scientist Carl June, who led its development.

The CAR T-cell treatment, manufactured by the drug company Novartis, initially would be available only for the small number of children and young adults whose leukemia doesnt respond to standard care. Those patients typically have a grim prognosis, but in the pivotal trial testing the therapy in almost a dozen countries, 83 percent of patients went into remission. A year later, two-thirds remained so.

And childhood leukemia is just the start for a field that has attracted intense interest in academia and industry. Kite Pharma of Santa Monica, Calif., has applied for FDA approval for aggressive non-Hodgkin lymphoma, and a similar Novartis application is close behind. Researchers also are exploring CAR T-cell therapys use for multiple myeloma and chronic lymphocytic leukemia, the disease that afflicted Ludwig. Theyre also tackling a far more difficult challenge using the therapy for solid tumors in the lungs or brain, for example.

The excitement among doctors and researchers is palpable. Were saving patients who three or four years ago we were at our wits end trying to keep alive, said Stephen Schuster, the Penn oncologist who is leading a Novartis lymphoma study. Both the study and a Kite trial have shown that the treatment can put about one-third of adults with advanced disease those who have exhausted all options into remission.

Yet along with the enthusiasm come pressing questions about safety, cost and the complexity of the procedure.

It involves extracting white blood cells called T cells the foot soldiers of the immune system from a patients blood, freezing and sending them to Novartiss sprawling manufacturing plant in Morris Plains, N.J. There, a crippled HIV fragment is used to genetically modify the T cells so they can find and attack the cancer. The cells then are refrozen and sent back to be infused into the patient.

Once inside the persons body, the T-cell army multiplies astronomically.

Novartis hasnt disclosed the price for its therapy, but analysts are predicting $300,000 to $600,000 for a one-time infusion. Brad Loncar, whose index fund focuses on cancer immunotherapy treatment, hopes the cost doesnt prompt a backlash. CAR-T is not the EpiPen, he said. This is truly pushing the envelope and at the cutting edge of science.

The biggest concerns, however, center on safety. The revved-up immune system becomes a potent cancer-fighting agent but also a dangerous threat to the patient. Serious side effects abound, raising concerns about broad use.

Treating patients safely is the heart of the rollout, said Stephan Grupp of the Childrens Hospital of Philadephia, who as director of its Cancer Immunotherapy Program led early pediatric studies as well as Novartiss global trial. The efficacy takes care of itself, but safety takes a lot of attention.

One of the most common side effects is called cytokine release syndrome, which causes high fever and flulike symptoms that in some cases can be so dangerous that the patient ends up in intensive care. The other major worry is neurotoxicity, which can result in temporary confusion or potentially fatal brain swelling. Juno Therapeutics, a biotech firm in Seattle, had to shut down one of its CAR T-cell programs because five patients died of brain swelling. Novartis has not seen brain swelling in its trials, company officials said.

To try to ensure patient safety, Novartis isnt planning a typical product rollout, with a drug pushed as widely and aggressively as possible. The company instead will designate 30to 35 medical centers to administer the treatment. Many of them took part in the clinical trial, and all have gotten extensive training by Grupp and others.

Grupp said he and his staff learned about the side effects of CAR T-cell therapy and what to do about them through terrifying experience that began five years ago with Emily Whitehead.

The young girl, who had relapsed twice on conventional treatments for acute lymphoblastic leukemia, was in grave condition. Grupp suggested to her parents that she become the first child to get the experimental therapy.

I said, Surely, this has been tried on kids somewhere else in the world, recalled her father, Thomas Whitehead of Philipsburg, Pa. But Steve said, Nope, some adults got it, but that was a different kind of leukemia.

After getting the therapy, Emilys fever soared, her blood pressure plummeted, and she ended up in a coma and on a ventilator for two weeks in the hospitals intensive care unit. Convinced his patient would not survive another day, a frantic Grupp got rushed lab results that suggested a surge of interleukin 6 was causing her immune system to relentlessly hammer her body. Doctors decided to give Emily an immunosuppressant drug called tocilizumab.

She was dramatically better within hours. She woke up the next day, her 7th birthday. Tests showed her cancer was gone.

The approval of CAR T-cell therapy would represent the second big immunotherapy advance in less than a decade. In 2011, the FDA cleared the first agent in a new class of drugs called checkpoint inhibitors. It has approved four more since then.

There are big differences between the two approaches. The checkpoint inhibitors are targeted at solid tumors, such as advanced melanoma, lung and bladder cancer, while CAR-T cell therapy has been aimed at blood disorders. And although checkpoint inhibitors are off the shelf, with every patient getting the same drug, the other is customized to an individual. Many immunotherapy experts think the greatest progress against cancer will occur when researchers figure out how to combine the approaches.

For the Penn team, the CAR T-cell story goes back decades, starting at the then-National Naval Medical Center in Bethesda, where June and a postdoc fellow named Bruce Levine worked on new HIV treatments. In the process, they figured out a way to turbocharge T cells to make them more powerful and plentiful.

The pair moved to Philadelphia in 1999 and dove into cancer research. Two years later, Junes wife died of ovarian cancer, something he has credited as spurring him to work even harder in the field. In the years that followed, researchers across the country, including at Memorial Sloan Kettering Cancer Center in New York and Fred Hutchinson Cancer Research Center in Seattle racked up an array of tantalizing discoveries involving T cells.

Fast-forward to 2010, when Ludwig, who lives in Bridgeton, N.J. became Penns first patient to receive CAR T-cell therapy. Two other men got the treatment not long after. One is still in remission; the other relapsed and died.

But after those three patients, the Penn researchers ran out of money for more treatments. To try to raise interest and funding, they decided to publish the results of their work. The article that appeared in the New England Journal of Medicine in August 2011 created a firestorm, June said one that brought them new resources. David Porter, a Penn oncologist working with June, was on vacation in western Maryland and had to stop at a Kohls to buy a dress shirt for the immediate TV interviews.

The pediatric trial opened the following spring with Whitehead. Six months later, Penn licensed its technology to Novartis in exchange for financial support, which included a new cell-manufacturing facility on campus.

With FDA approval seeming imminent, the researchers who were so instrumental in the therapys development and testing are almost giddy. Grupp is especially pleased that the advance will be available first to children. Usually everything is developed first for adults, he noted recently, and children are an afterthought.

Read more:

This is not the end: Using immunotherapy and a genetic glitch to give cancer patients hope

This 8-year-old is free of cancer for now after a breakthrough treatment

For a 6-year-old with cancer, a future staked on medicines hottest field

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First gene therapy ‘a true living drug’ on the cusp of FDA approval – Washington Post

Smelling food linked to weight gain in new study – The Independent

Smelling food before eating it has been linked to weight gain in new research.

In a study using mice, US researchers found that the smell of food could playan important role in how the body processes calories.

To make their findings, researchers at the University of California, Berkeley, used gene therapy to cut off the sense of smell in a group of obese mice.

The scientists found that mice who couldn’t smelllost weight compared to those who could.However, the team were surprised to find that the slimmer mice who were unable tosmell alsoate the same amount of high-calorie food as mice who could. In addition, the mice who were able to smell doubled in weight. Mice with a boosted sense of smell, meanwhile, put on the most weight.

Smelling food could lead the body to store it rather than burn it off, the team believes.

This paper is one of the first studies that really shows if we manipulate olfactory inputs we can actually alter how the brain perceives energy balance, and how the brain regulates energy balance, said Cline Riera, ofCedars-Sinai Medical Center in Los Angeles.

The researchers behindthe study published in the journal Cell Metabolism hope it could help those who develop eating disorders including anorexia due to age, injury or developing diseases such as Parkinsons. It could also help those who struggle to lose weight, they added.

Sensory systems play a role in metabolism. Weight gain isnt purely a measure of the calories taken in; its also related to how those calories are perceived, said senior author Andrew Dillin, the Thomas and Stacey Siebel Distinguished Chair in Stem Cell Research, professor of molecular and cell biology and Howard Hughes Medical Institute Investigator. If we can validate this in humans, perhaps we can actually make a drug that doesnt interfere with smell but still blocks that metabolic circuitry. That would be amazing.

For that small group of people, you could wipe out their smell for maybe six months and then let the olfactory neurons grow back, after theyve got their metabolic program rewired, Dillin added.

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Smelling food linked to weight gain in new study – The Independent

Ipswich mom honored as Science Super Hero – The Salem News

IPSWICH An Ipswich mom has been crowned a Science Super Hero by the Science Channel.

Jocelyn Duff was recognized as the June honoree of the networks monthly initiative for furthering science in her community and encouraging the next generation of innovators and problem solvers.

Duff, a physicians assistant, is the founder and executive director of CureCMT4J, an all-volunteer, nonprofit foundation inspired by her 11-year-old daughter, Talia.

In 2015 Talia was diagnosed with Charcot Marie Tooth Type 4J (CMT4J), a rare disease known to affect approximately 22 people worldwide. The neuro-degenerative disease, like ALS, causes progressive muscle weakness, leading to paralysis and respiratory compromise.

Duff founded CureCMT4J in June 2016 to address an expedited path toward a gene therapy cure. She quickly assembled a scientific team of world experts who began pre-clinical work in October 2016 at Jackson Laboratories, through a grant from the National Institute of Health.

In December 2016, CureCMT4J funded the first viral vector production for CMT4J through the University of North Carolina-Chapel Hill. Duff expects proof of concept results this summer. CureCMT4Js goal is to reach a human clinical trial as quickly as possible to save Talia and help others afflicted with rare diseases.

The Science Channel nominates three Science Super Heroes monthly from any of the following categories: Super Star (CEO or professional), Shooting Star (super fan), and Rising Star (college student). Each Science Super Hero is highlighted on-air on Science Channel the first Thursday of the month and across all Science Channel social platforms for the entire month.

To learn more about CMT4J or to donate towards a cure go to

Mary Markos may be contacted at 978-675-2708 or


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Ipswich mom honored as Science Super Hero – The Salem News

Gene Editing Controversy Reminds Us Just How Much Money Influences Science – Gizmodo

Recently, a kerfuffle in the world of CRISPR illustrated just how easily moneyand our perception of itcan impact science.

In late May, a paper came out questioning how effective the gene-editing technology really is. Working with mice, researchers found that edits made with CRISPR can also result in thousands of unintended changes to a genome. The study cast serious doubt on whether CRISPR is ready for prime time.

The fallout was swift. Stock prices of three CRISPR companiesEditas Medicine, Intellia Therapeutics and CRISPR Therapeuticstumbled. Scientists affiliated with those companies fired back, questioning the studys methodology. Stocks bounced back. The scientific world was set atwitter, questioning not only the validity of the initial study, but how to trust a rebuttal against that study when it came from those who stood to lose the most from its publication.

Conflicts of interest arent a new problem in science. One frequently-cited example is the role that tobacco industry-funded scientists played in distorting the health consequences of smoking. There is a significant body of evidence suggesting financial interests can correlate with favorable results. But, conflicts of interest arent always all bad. Research funding from sources with a vested interest in a topic can sometimes help advance science that otherwise might not get funded at allthink the patient advocacy groups funding cures for little-known diseases.

Whats undoubtedly true is that money plays a significant role in science. And rarely has there been as much money at stake as with CRISPR, the nascent gene-editing technique that promises to cure everything from genetic disease to global famine by allowing researchers to easily cut and paste particular genes. When scientists whose fortune and reputation hinges on a particular technology speak out against a paper questioning that technology, its hard not to wonder how that bias might factor in.

There is this unspoken assumption the people in academia are driven primarily by the quest for knowledge and the science, Josephine Johnston, a bioethicist at The Hastings Institute, told Gizmodo. But in recent history, controversies over things like tobacco and GMOs have begun to erode that perception. When it became clear that more and more scientists have a specific financial stake, it caused a lot of concern, Johnston said.

When it comes to CRISPR, the financial stakes are certainly complicated. Two separate groups of scientists have long been embroiled in a battle over the patent for the technology, with one headquartered at The Broad Institute of MIT and Harvard, and the other at U.C. Berkeley (so far, the US has awarded the patent to Broad but Europe and China have sided with Berkeley). The patent gives the scientists the ability to license the technology. In this case, Broad has licensed the technology to Editas, a company founded by scientists at both Berkeley and Broad. Berkeley licensed its patents Intellia, which Berkeleys Jennifer Doudna is also a founder of, as well as to CRISPR Therapeutics.

Most of the headline-grabbing scientists associated with CRISPR have major financial stakes in publicly traded CRISPR companies, creating a strong incentive across the industry for CRISPR to succeed. The concern is that a CRISPR-favoring bias could potentially cause researchers to misinterpret or skew study results, or forge ahead with human clinical trials before CRISPR is really ready.

Thats not to say that theres necessarily anything wrong with the points industry-affiliated CRISPR scientists raised in their rebuttal to the paper questioning their science. In fact, several other scientists raised similar concerns.

Finances certainly can influence science. Not just companies, but also the premises supporting government grant finances, George Church, an author of the rebuttal paper and founder of Editas, told Gizmodo via email. We were basically raising issues that the original authors can address. This, fortunately, doesnt require perfect unbiased authors. Anyone can point out a potential problem.

Michael Kalichman, director of UC San Diegos research ethics program, pointed out that financial interest isnt the only bias that scientists have to be wary of.

Weve talked about conflicts of interest for many years in science and for many reasons much of that focus has been on financial conflicts. For one, its easy to see, he told Gizmodo. What I find astonishing is that even scientists forget that there are other conflicts that can influence work, like tenure, your reputation or just being excited about an idea.

Kalichman said his biggest concern is less that scientists are actually doing anything unethical, and more that financial conflicts of interest create the perception that they are. The paper that sparked the CRISPR controversy received press in most major news outlets, and the blowback against it has received significant attention, too.

Part of me is worried about the way [this CRISPR fight] is playing out because of the picture it paints of science, he said. We have this battle going on in the pages of scientific journals that creates this perception that this is what science is about when most of science is not about this.

Johnston echoed those concerns.

The introduction of these financial interests muddies the water enough that people dont know who to trust, she said. Whether or not we can see anything wrong with either study, or anyone else can, theres still this suspicion that the financial stakes must have played some role here. Thats a very corrosive thing across science.

In the initial Nature Methods paper, scientists from Stanford and University of Iowa working to cure blindness in mice found that while CRISPR did successfully edit the gene for blindness, it also caused mutations in more than a thousand unrelated genes. The consequences of those off-target effects, far more extensive than previously realized, are largely unknown. This finding warns that CRISPR technology must be further tailored, particularly before it is used for human gene therapy, the researchers wrote.

As mentioned, scientists associated with CRISPR companies were not the only ones, or even the first, to criticize the studys design. Many scientists raised red flags about basic mistakes, such as misidentifying genes, mislabeling genetic defects, and the small number of animals the researchers had included in their research. But other scientists found the reaction against the paper, was written as a brief letter to the editor intended mainly to point to an area where more study might be needed, to be overwrought. Some, like UC Davis professor Paul Knoepfler, suggested the real problem was that the results had been over-interpreted and blown up in the press, setting in motion an out-sized blowback.

Scientists from Intellia and Editas both sent separate letters to Nature Methods, forcing it to eventually add a note to the study about the controversy surrounding the letter. Whats more, in publishing their own study taking down the initial works methodology, scientists associated with Editas opted to publish a pre-print online before it was peer-reviewed, though the initial paper did go through a peer review process. And while the response paper mentions the institutions and companies each author is affiliated with, there is no clear conflict of interest section. (Church said conflicts of interest will be included with journal publication.)

This week, a pre-print of a second paper published by scientists at Intellia that reanalyzed the original papers data and found far fewer off-target edits also appeared online.

In a statement, the Broad Institute said that the peer review process should weed out the impact of any conflict.

Scientific paperswhether making a new claim, or analyzing an existing scientific claimshould always be subject to rigorous evaluation by the scientific community to establish whether the scientific evidence actually supports the argument in the paper, the Broad Institute told Gizmodo. Such review by the community provides protection against incorrect arguments, whether due to a scientific error, financial or reputational interest, or something else.

Most journals and research institutions have a comprehensive conflict of interest policy. In 2010, UNESCO called for journals to adopt a common standard of dealing with the complex and growing financial arrangements that have developed in recent years between vested interests and independent scientists. Even so, sometimes those ties wind up omitted.

Kalichman said more might be needed to address conflicts of interest in the realm of basic science.

In clinical research, you do everything you can to separate financial interests from the people doing the work, Kalichman said. We dont really talk about that in basic research, but maybe we need to do something like that. Maybe if you have a financial interest, youre not the one that looks at the raw data.

Its next to impossible to fully weed out conflict in sciencebe it financial or otherwise. Besides, it makes sense that scientists should be able to make money off of their own work. But its also impossible not to acknowledge that those interests can influence the science. How could they not?

Update: This story has been updated to include mention of the Intellia study.

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Gene Editing Controversy Reminds Us Just How Much Money Influences Science – Gizmodo

Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of … – GlobeNewswire (press release)

July 06, 2017 07:00 ET | Source: Shire Pharmaceuticals Group

Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of Hemophilia A

SHP654 aims to deliver sustained protection against bleeds for patients with hemophilia A

Lexington, Mass.-July 6, 2017- Shire plc (LSE: SHP, NASDAQ: SHPG), the leading biotechnology company focused on serving people with rare diseases, today announcedthe submission of an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for SHP654, also designated as BAX 888, an investigational factor VIII (FVIII) gene therapy for the treatment of hemophilia A. SHP654 aims to protect hemophilia A patients against bleeds through the delivery of a long-term, constant level of factor expression.1 The IND filing for SHP654 represents the latest step forward for Shire’s gene therapy program, which shows promise for both hemophilia A and B populations.

“Shire is leveraging decades of scientific leadership in hemophilia to advance research in gene therapy for this community,” said Paul Monahan, M.D., Senior Medical Director, Gene Therapy, Shire. “Drawing from our rich heritage, Shire is well equipped to sustainably support the development of gene therapies that aim to advance current standards of care and minimize the burden of this disease. SHP654 uses a proprietary technology platform designed to produce sustained levels of factor similar to the natural mechanisms of the body. Our goal with gene therapy for hemophilia is to uphold the highest standards for safety and efficacy.”

Shire’s gene therapy program for hemophilia A uses a recombinant adeno-associated virus serotype 8 (rAAV8) vector, which selectively targets the liver.1,2 It involves the delivery of a functional copy of FVIII to the body’s liver to enable its own production of FVIII, rather than relying on a factor-based treatment.1 SHP654 uses the rAAV8 vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1 The FVIII expression is further controlled in patients by incorporating the liver-specific transthyretin (TTR) promoter/enhancer.1

The IND filing for SHP654 was based on the results of pre-clinical and phase 1 studies demonstrating the potential utility of this candidate, including the following that will be presented at the International Society on Thrombosis and Haemostasis (ISTH) 26th Biennial Congress in Berlin, Germany, from July 8 – 13, 2017:

An IND is a request for FDA authorization to administer an investigational drug to humans.5 Following the FDA’s acceptance of the IND for SHP654, Shire will study SHP654 in a global multi-center study evaluating safety and examining the SHP654 doses required to boost factor VIII activity levels and affect hemophilic bleeding and will pursue bringing this innovation to markets worldwide.

About SHP654 Shire is developing SHP654 (BAX 888), which includes technology acquired from Chatham Therapeutics, LLC, a spin-out of Asklepios Biopharmaceutical, Inc. SHP654 is an investigational factor VIII (FVIII) gene therapy intended to treat hemophilia A using a recombinant adeno-associated virus serotype 8 (rAAV8) vector to deliver a codon-optimized, B-domain deleted FVIII (BDD-FVIII) specifically to a patient’s liver, where FVIII would then be produced and used to manage bleeds.1,2

About Hemophilia A Hemophilia A, the most common type of hemophilia, is a rare bleeding disorder that causes longer-than-normal bleeding due to lack of clotting factor VIII in the blood.6 The severity of hemophilia A is determined by the amount of factor in the blood, with more severity associated with lower amounts of factor.7 More than half of patients with hemophilia A have the severe form of the condition.7 Approximately 25-30% of individuals with severe hemophilia A develop inhibitors.8 Inhibitors are a serious medical problem that can occur when a person with hemophilia has an immune response to treatment with clotting factor concentrates.9 Hemophilia primarily affects males, with an incidence of one in 5,000 male births.7,10



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About Shire

Shire is the leading global biotechnology company focused on serving people with rare diseases and other highly specialized conditions. We strive to develop best-in-class products, many of which are available in more than 100 countries, across core therapeutic areas including Hematology, Immunology, Neuroscience, Ophthalmics, Lysosomal Storage Disorders, Gastrointestinal / Internal Medicine / Endocrine and Hereditary Angioedema; and a growing franchise in Oncology.

Our employees come to work every day with a shared mission: to develop and deliver breakthrough therapies for the hundreds of millions of people in the world affected by rare diseases and other high-need conditions, and who lack effective therapies to live their lives to the fullest.

Forward-Looking Statements

Statements included herein that are not historical facts, including without limitation statements concerning future strategy, plans, objectives, expectations and intentions, the anticipated timing of clinical trials and approvals for, and the commercial potential of, inline or pipeline products, are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire’s results could be materially adversely affected. The risks and uncertainties include, but are not limited to, the following:

a further list and description of risks, uncertainties and other matters can be found in Shire’s most recent Annual Report on Form 10-K and in Shire’s subsequent Quarterly Reports on Form 10-Q, in each case including those risks outlined in “ITEM 1A: Risk Factors”, and in Shire’s subsequent reports on Form 8-K and other Securities and Exchange Commission filings, all of which are available on Shire’s website.

All forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by this cautionary statement. Readers are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Except to the extent otherwise required by applicable law, we do not undertake any obligation to update or revise forward-looking statements, whether as a result of new information, future events or otherwise.

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Shire submits investigational New Drug Application to FDA for Gene Therapy candidate SHP654 for treatment of … – GlobeNewswire (press release)

Girl who threw first pitch aims to strike out disease affecting her 3-year-old sister – The Sun Herald

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Girl who threw first pitch aims to strike out disease affecting her 3-year-old sister
The Sun Herald
She threw the pitch, which was sponsored by the Sun Herald, hoping it would help strike out multiple sulfatase deficiency or MSD, a rare genetic disease affecting her sister, 3-year-old Willow Cannan. MSD affects … While Willow will not make the trip

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Girl who threw first pitch aims to strike out disease affecting her 3-year-old sister – The Sun Herald

With a son who is legally blind, Lisa Pleasants works to raise funds for research – Florida Times-Union

Even while she was pregnant with her son Brendon, now 18, Lisa Pleasants knew there was a possibility he would be born with a rare genetic condition that could leave him legally blind.

Pleasants has two brothers and a cousin who were born with X-linked retinoschisis, which causes layers of the retina to separate. It is the leading cause of juvenile macular degeneration in males.

Brendon Pleasants is legally blind. He uses magnifiers, large-print books, a camera connected to a computer, a Galaxy S6 cell phone and an iPad to read. Without assistance, he can read the top two lines of an eye chart. But his vision is getting worse over time, he said.

A recent graduate of Mandarin High School, Brendan was an honor roll student who ran track and cross country and earned a black belt in karate.

His mom is founder of MOMS for Sight, a nonprofit working to fund research into and raise awareness about retinal degenerative diseases.

MOMS for Sights primary fundraiser is its annual Black Ties &Blindfolds gala. MOMS for Sight also participates in the Foundation Fighting Blindnesss annual Vision Walk and sells MOMS for Sight bracelets through the website, where she also writes an occasional blog.

This year MOMS for Sight raised $18,000, part of $86,000 raised in Jacksonville for the Foundation Fighting Blindness.

Both Lisa and Brendon Pleasants see gene therapy as their hope for the future. His condition is caused by the lack of a certain protein. They have been excited about the research into gene therapy being done by William W. Hauswirth, a professor of ophthalmology at the University of Florida. Hauswirth is an innovator of delivery systems for sight-saving gene therapies that could provide the missing protein.

In April 2016, MOMS for Sight honored Shannon Boye, an assistant professor in University of Florida Department of Ophthalmology, who works with Hauswirth, with its MOMS for Sight Visionary award during the Black Tie &Blindfolds gala.

Last winter, Brendon was initially accepted into a gene therapy trial in Boston. But testing revealed that he had high pressure in his eyes, something hed never had before.

High eye pressure is a warning sign for glaucoma and Brendon had to leave the trial and return to Jacksonville to get laser treatment for his glaucoma.

In one of her MOMS for Sight blogs, Lisa Pleasants wrote about their disappointment at not starting the trial: This post is most likely the hardest one Ive ever written and it has taken me a few weeks to gather my emotions . We were absolutely crushed . The doctor in Boston told us, as he saw my tears forming, that everything happens for a reason and that we should be thankful we found this new issue early. I am thankful.

The Pleasant are hopeful Brendon will eventually get admitted to a trial. In the meantime, hes preparing to head to Orlando to attend the University of Central Florida, where he wants to study engineering.

His goal is to become an aerospace engineer. Hes been fascinated by the space program since he was a little boy.

When he was 4 years old, Lisa Pleasants said, he told me, I dont want to be on the rocket that goes into space. I want to build the rocket that goes into space.

At UCF, Brendon Pleasants will live in a dorm. Hes confident hell have no difficulties finding his way around campus. If he wants or needs to go somewhere off campus, he can call for an Uber or catch a ride with friends. Hes looking forward to the experience.

I like feeling independent, he said.

Charlie Patton: (904) 359-4413

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With a son who is legally blind, Lisa Pleasants works to raise funds for research – Florida Times-Union

Researchers identify novel mechanism underlying efficacy of common heart failure drug – Medical Xpress

July 3, 2017 Credit: CC0 Public Domain

Beta-blocker drugs serve a key role in the treatment of heart failure, preventing bombardment of the heart by catecholamines – substances like epinephrine and norepinephrine – which overexcite and stress the heart. But not all heart failure patients respond to beta-blockers, for reasons that have been unclear. Now, in new work, researchers at the Lewis Katz School of Medicine at Temple University (LKSOM) show that dysfunction of beta-adrenergic receptor 3 (3AR) – a novel beta-blocker target – and consequent decreases in a critical cardioprotective phospholipid may be to blame.

The cardioprotective molecule, known as sphingosine 1-phosphate 1 (S1P), keeps heart cells from dying following events such as heart attack and heart failure. “The higher the levels of S1P in heart failure, the better the outcome,” explains Walter J. Koch, PhD, W.W. Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology and Director of the Center for Translational Medicine at LKSOM, as well as senior investigator on the new study.

According to Dr. Koch, beta-blocker drugs increase S1P levels by attenuating hyperactive beta-adrenergic receptor signaling, with most of the drugs acting selectively on 1ARs. “But the drugs can also have stimulatory effects on 3AR, promoting 3AR activity,” he says. “Our new work shows that when 3AR is dysfunctional, the protective effects of S1P are lost.”

The findings were published online July 3 in the Journal of the American College of Cardiology.

“Our group has spent more than a decade investigating beta-blocker mechanisms,” explains Alessandro Cannavo, PhD, a research associate in the Center for Translational Medicine and Department of Pharmacology at LKSOM and lead author on the new report. “We know that a kinase called GRK2 that is downstream of beta-adrenergic receptor activation is responsible for downregulation (decreased production) of the S1P receptor 1 (S1PR1), which functions in cardioprotective signaling. We have also demonstrated in rats that restoration of S1PR1, via gene-therapy, can correct heart failure.”

In their new study, Dr. Koch and colleagues looked more deeply into the mechanisms driving S1PR1 downregulation in heart failure, as well as the effects on S1P of metoprolol, a commonly used beta-blocker drug. Experiments in cells exposed to isoproterenol (to mimic the condition of heart failure) showed that treatment with metoprolol prevented S1PR1 downregulation. Microscopic studies revealed that whereas isoproterenol triggered S1PR1 internalization, with receptors retreating from their active front at the cell surface into the interior of the cell, metoprolol produced the opposite effect.

The researchers further showed in mice that treatment with either metoprolol or S1P effectively halts heart failure progression following heart attack. To determine whether those effects were related to 3AR, Dr. Koch’s team performed a series of experiments in 3AR knockout mice. S1P levels remained low in 3AR knockout animals, despite treatment with metoprolol. Moreover, in the absence of 3AR, metoprolol failed to ameliorate cardiac damage suffered post-heart attack, whereas metoprolol improved cardiac function after heart attack in mice with normal 3AR expression.

Analyses of samples from heart failure patients taking 1AR blockers confirmed the clinical relevance of the findings. Compared to untreated patients, circulating levels of S1P were significantly elevated in patients that had been treated with the drugs.

“In the concept of precision medicine, our study suggests that altered 3AR or S1P signaling can be responsible for the diverse response to beta-blockers between human patients usually observed in clinical practice,” says Dr. Cannavo.

“Mechanistically, we’ve identified a novel means by which 1AR blockers prevent the progression of heart failure, whereby 3AR must be active for metoprolol to work,” adds Dr. Koch.

The team plans next to explore the effects of beta-blockers that lack activity at 3AR.

Explore further: Some heart attack patients may not benefit from beta blockers

Contracting shingles, a reactivation of the chickenpox virus, increases a person’s risk of stroke and heart attack, according to a research letter published today in the Journal of the American College of Cardiology.

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Researchers identify novel mechanism underlying efficacy of common heart failure drug – Medical Xpress

After raising $50M, virtual gene therapy startup sets up shop in Cambridge – Boston Business Journal

Boston Business Journal
After raising $50M, virtual gene therapy startup sets up shop in Cambridge
Boston Business Journal
LogicBio Therapeutics becomes the latest local entrant to the field of gene therapy, a method of inserting healthy genes into cells to replace missing or faulty ones. … Research the 3+ year digital archive, and People on the Move leads database download.

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A Cure for Clara – The Alcalde

By Rose Cahalan in Features, July | August 2017 on July 1, 2017 at 9:00 am |

From left, Jenny, Tanner, Clara, and Ryan Bragg. Credit: Tiffany Roach

In the video, Clara Bragg and her mom, Jenny, are sitting underneath the family Christmas tree.

Clara, 2, wears a pink bow in her wispy blonde hair. She smiles before turning to play with a pile of colored blocks, her mouth hanging open in concentration. Its an idyllic family scene, complete with Claras brother, Tanner, 5, sitting next to her under the warm glow of the tree. Then in the next scene, the whole family is seated together on the couch, Jenny with a squirming Clara on her lap while her husband, Ryan, MBA 10, holds Tanner on his knee. Hello, he says, looking into the camera. My name is Ryan Bragg, and this is my family.

By now, the Braggs are used to introducing themselves to the world. Theirs is a story theyve told hundreds of timesin YouTube videos like this one, on the local news, on websites and Facebook posts and forums, and at dinners, parties, and fundraisers. Its not an easy story to tell, but after eight months of practice, they are pros. So they dont hesitate when theyre asked to tell it one more time.

Clara was born in April 2014, and the Braggs were over the moon, according to Jenny, BS 03. Theyd always wanted a boy and a girl, and her arrival made their family feel complete. She was an energetic baby with lots of personality. She was constantly moving, Jenny says. Always wiggling, always wanting to be in the mix. A very social kid. She hit all her developmental milestones, including saying mama and dada. But then, around 14 months, she stopped saying them. She also couldnt quite get the hang of walking and often fell.

The Braggs started to wonder if something was wrong. Clara had always been tall for her age; maybe her balance just hadnt caught up to her height. They took her to doctors and physical therapists near their home outside Birmingham, Alabama. Each test and exam led to more referrals, shrugs, and vague reassurances. We saw more specialists than I can count, Ryan says, and every single one of them said a different version of the same thing. Yeah, there are some delays, but its not a big deal. Either shell outgrow it, or well handle it with therapy.

After a year of these appointments, the Braggs enrolled Clara in a study that involved a full genetic workup. A genetic counselor and a geneticist called them in for a meeting to discuss the results. They were pretty direct about it, Jenny remembers. He told us what was going to slowly happen, and that she probably wouldnt

She pauses, and theres a long silence before Ryan starts talking. The geneticist told them that Clara had a disease called GM1 gangliosidosis that would cause her to slowly lose her ability to walk, talk, and eat; to suffer breathing difficulties, seizures, deafness, and blindness; and eventually, to die before her 10th birthday. And, Oh, by the way, just go home and watch that happen because you probably only have a few years left, Ryan says. It hits you like a ton of bricks. Theres no escaping the devastation and the lump in your throat and the knots in your stomach.

The genetic counselor handed them a three-page printout with more information. They learned that GM1 is extremely rare, affecting 1 in 200,000 children, and that there is no cure. It was pretty obvious that theyd done the medical equivalent of Googling this thing, Ryan says.

Which is exactly what the Braggs did when they got home. They found medical journals and forums and websites and pictures of kids transforming from smiling babies into bedridden toddlers with breathing tubes. They also came across the website of Doug Martin, a research scientist and professor at Auburn Universitys College of Veterinary Medicine, who studies GM1 and related neurodegenerative diseases. Ryan fired off an email. We are just beginning to learn about and try to understand this disease, but have learned of the research you and your team have done Would it be possible to meet? he wrote. This is quite a shock to us and were starting from scratch.


On the first and second floors of the Scott-Ritchey Research Center at Auburn University in Auburn, Alabama, there are more than 100 cats. As research animals go, they live a comfortable life: A full-time staffer is dedicated to their care, playing with them and making sure they get enough exercise. They nestle into towel-lined boxes, scamper up to high perches, and bat at toy mice with their paws.

Back in 2003, this scene looked very different. As kittens, the lab cats developed minor tremors that soon progressed into full-body shakes. Soon they couldnt stand or walk; an employee had to lift them into the litter box. These cats were born with GM1, and gene therapy saved their lives.

The results have been tremendous, Martin says. They arent completely normal, but if I put them in a room with a bunch of normal cats, it would be hard for you to pick them out. They have only a slight hind-limb weakness.

Before Martins team injected an engineered virus directly into the cats brains, their life expectancy was 8 months. Now some cats in the colony are 7 years old. The average survival increase is six times, which is really unheard of, he says.

GM1 falls within a category of rare diseases known as lysosomal storage diseases. Lysosomes are the digestive system of the bodys cellssacs of enzymes that break down molecules and send them elsewhere in the body for recycling. Kids (and cats) with GM1 dont make enough of a critical enzyme, and without it, the recycling process comes to a halt. That leads a protein called GM1 ganglioside to build up to toxic levels in the brain and other parts of the body.

The earlier GM1 strikes, the more severe it is. Clara was diagnosed with Type 2, the late infantile type. Most kids with that variant of the disease die before they finish elementary school.

Researchers at Auburn have been studying GM1 for more than 30 years. Martins predecessor and graduate school mentor, Henry Baker, kept the cat colony in his garage as he experimented with treatments, such as injecting the missing enzyme. Baker eventually succeeded in treating the cats peripheral organs, but he couldnt get past the blood-brain barriera security system of sorts that protects the brain from foreign invaders. After decades of work, Martin and his colleagues have overcome that obstacle by engineering a virus that can pass through the barrier. An injection directly into the brain is no longer requireda simple one-time IV dose will do the trick. Once the virus is in the body, it starts churning out the enzyme that kids like Clara need, Martin says.


On a Saturday afternoon in August, Martin was at home when he saw Ryan Braggs email. It was only the latest of dozens of desperate messages hes received from parents over the years. Now that were closer to a clinical trial, I hear from parents every couple of weeks, Martin says. The Braggs were the second GM1 family hed met in Alabama. A year earlier, Martin had gotten to know Porter Heatherly, a toddler with the most severe type of the disease. I had never watched a child deteriorate on a monthly or weekly basis the way I did with Porter, he says. Heatherly died in November 2016.

Martin called the Braggs back within a half-hour. Awe and respect are audible in Ryans voice as he recalls the conversation. I was impressed that he called at all, Ryan says. Hes a busy guy at a top university. He called to offer his condolences and to give us a glimmer of hope. In the coming months, they would meet Martin and visit his lab.

The Braggs learned that Claras diagnosis had come at a fortuitous time. Martin was already close to setting up a clinical trial in humans. After decades of working on the science, he felt confident in the gene therapys potential to help kids as it had cats. Now the biggest barriers were bureaucracy and funding.

GM1 is one of more than 7,000 rare diseases affecting at least 25 million Americans. More than half of rare disease patients are children, and 80 percent of rare diseases are genetic. In the medical community, these are sometimes called orphan diseases for their lack of funding and attention. With many of these conditions affecting maybe a few dozen people or fewer, there just cant be enough funding from traditional sources, says Mary Dunkle, vice president of educational initiatives for the National Organization for Rare Disorders. In many cases, most or even all of the research funding is raised by the patient community.

In the case of GM1, the most costly part of a clinical trial would be manufacturing the virus for the gene therapy. A much larger quantity of the virus is needed for a human trial than in animals, and scaling it up isnt cheap. Martin estimated the total manufacturing cost at $750,000.

That was all the Braggs needed to hear. They set out to raise as much money as they could as quickly as possible. In order to be eligible for the trial, Clara would still need to be fairly early on in her disease progression. The clock was ticking.

Theres something unimaginably cruel about busy working parents, still reeling from traumatic news, having to take on what amounts to a second full-time jobbut the Braggs felt they didnt have a choice. They threw themselves into their new roles as GM1 advocates and fundraisers. In a sense, they were as well-prepared as anyone could be. Jenny studied corporate communications at UT, so messaging and social media marketing were familiar territory. Shed planned events in her former job at the Texas General Land Office, experience that would come in handy for the dozens of fundraisers ahead. Ryans MBA from McCombs taught him how to tap into his network and hit financial goals. Jenny quit her job to focus on caring for Clara and fundraising, while Ryan juggled work as a finance director at PepsiCo with the second shift at home.

Jenny rattles off a litany of tactics. Weve had a fashion show, a movie theater event, all kinds of dinners, silent auctions, raffles, a St. Patricks Day campaign called Buck for Luck, she says. We did charity beers, a wiffle ball tournament, a daddy-daughter dance, and a crawfish boil. The whole spectrum, really. The A Cure for Clara Facebook page has more than 1,300 likes.

Credit: Magen Davis

Their work has paid off. In less than a year, the Braggs have raised more than $1 million for GM1 research. Those funds have directly contributed to making a clinical trial possible. Theyve knocked it out of the park, Martin says. Ryan and Jenny are amazing. For me, its been so great to not have to worry about funding as much. Its enabled me to focus on the science.

It takes six months to make the viral vector for the clinical trial, and that process cant begin until the scientists have shown they can pay for it. With a typical National Institutes of Health grant taking 18 months to get funded, Martin says the trial process would be months and months behind without the Braggs donation. Now things are well underway, and the researchers are hoping the trial will take place in December 2017 or January 2018.

At the end of my conversation with the Braggs, I ask if theres anything other stories have gotten wrong. Everyone feels compelled to say were searching for a cure, Jenny says. But its such a key component to our campaign that were actually trying to fund the cure, not find the cure. Weve already found it.


Is that really true, though? While the cat research is promising, there is no guarantee that animal results will translate directly to humans, and many questions about the disease remain unanswered. Martin is more measured. Cure is a really strong word, he says. I feel very strongly that our work will benefit the human patients. That said, until you actually try it, you just dont know for sure. He adds, I know that the parents are desperate. The pressure we feel is enormous.

One important unknown: whether the gene therapy in the trial will reverse symptoms or only halt the diseases progression. The results of animal studies have been mixed on that front, Martin says. Im hopeful there will be some recovery of function, he says, but nobody knows the answer at this point.

If the clinical trial has outstanding results, its possible the FDA will broaden it to include more patients. Should all go well, parents may then petition the agency to release the treatment under a provision called compassionate use. Also called right-to-try, compassionate use gives terminally ill patients access to new and experimental drugs. This legal loophole has saved lives, but its not without risks.

In 2014, the family of Josh Hardy, a 7-year-old cancer patient, ran a successful social media campaign to get him a drug through compassionate use. Media coverage at the time attacked the pharmaceutical company, Chimerix, for withholding the medicine. Eventually the company and the FDA relented, and the Chimerix CEO was fired. The drug saved Hardys life. But what if it hadnt? Had Hardy died after taking the drug, it would have been banned. That could potentially result in the deaths of innumerable future patients, bioethicists argued at the time, and we have an ethical responsibility to them, too. (Hardy died two years later of complications from his cancer.)

In a critical op-ed for, NYU medical ethicist Arthur Caplan argued that Hardys campaign went viral because he was a cute and cuddly childmuch like Clara, with her blond curls and cherubic smile. His parents, like the Braggs, are privileged, well-connected, and media-savvy. What about patients who lack those advantages? Another ethicist, George Annas, told Harpers that this whole community going-on-a-vengeance thing is not a decent way to get health care for your child.

Then theres the name forever on the minds of Martin and all gene therapy researchers: Jesse Gelsinger. Gelsinger died at age 18 during a botched gene therapy trial at the University of Pennsylvania in 1999. That was a tragedy, and it shut down our field for years, Martin says. We want to give these kids a chance, but we also dont want to do anything that could shut down a promising field. The FDA is always slowing us down, and although that can be very frustratingultimately, its a good thing. (Martin stresses that gene therapy has advanced significantly since 1999, and that the type of therapy used in the GM1 trial is as safe as it gets.)

Theres one final hurdle: drug pricing. Even if the trial goes well and the therapy is eventually approved, drugs for rare diseases tend to be extremely expensive. Thats because pharmaceutical companies are profit-driven, and its hard to turn a profit if your market consists of only a few dozen patients. The Orphan Drug Act of 1983 gave companies a financial incentive to make drugs for rare diseases, but prices have ballooned out of control: In 2014, the average orphan drug cost $118,820 per patient per year. That means families campaigning may not end even once theyve found and funded the cure. In 2016, the FDA approved a new drug for spinal muscular atrophy, another progressive and often fatal genetic disease in childrenbut it costs $750,000 a year, and insurance companies dont always cover it. Dozens of pleading GoFundMe pages have popped up.

Long-term, there absolutely needs to be a comprehensive look at reform for both the pricing and access issues, says Dunkle, the rare diseases advocate. Social media is powerful. It levels the playing field, gives families with rare diseases a way to make their voices heard. But sick kids shouldnt have to rely on Facebook to get life-saving care.


In April, the Braggs are gearing up for one of their biggest events yet: Claras third birthday party. The fundraising goal is $10,000; there will be VIP sponsors, a silent auction, live music, and cake with pink frosting. The next month, theyre planning a Zumba fun-raiser. Talking about their work, Ryan and Jenny sound hopefulbut also completely and utterly exhausted.

The balance is not great right now, Jenny admits. Its not great in terms of any aspect of our life and relationships and family. She and Ryan struggle to strike an impossible balance between constantly working to give their daughter a future and simply enjoying the time they have with her today. I wouldnt be able to live with myself if I wasnt putting everything I had into this, she says. But once this next fundraiser is over, weve said we need to take a break.

The Braggs worry about their older child, Tannerwith all the attention on his sister, is it even possible to give him a normal childhood? Hes only 5, and they arent sure how much he understands about the situation. They make a point to fit in his T-ball practices and take him to playdates. We try to prioritize him, to spend one-on-one time, Jenny says. But its a lot of energy that goes into Clara.

The night before our interview, Jenny says, Tanner blurted out a question as she was tucking him into bed. Is Clara going to die? She paused, taken aback, then decided she might as well tell him the truth: She will if we dont get her medicine in time.

Illustration by Jonathan Bartlett

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A Cure for Clara – The Alcalde

Artistry of Wine – Daily North Shore

HIGHLAND PARK The Foundation Fighting Blindness, the worlds largest private funder of sight-saving retinal disease research, hosted the 16th Annual Artistry of Wine on June 22 at the Highland Park Country Club. The 242 attendees enjoyed tastings from some of the top restaurants in the Chicagoland area along with a silent auction and a sweepstakes drawing to win a chance to drive a new Tesla SUV for a long weekend.

The event raised $89,000 to support the Foundations mission to advance research into preventions, treatments and cures for blinding retinal diseases including age-related macular degeneration (AMD) and retinitis pigmentosa (RP) that affect more than 10 million Americans, young and old. As promising treatments move into critical human studies, the need for research funding is greater than ever.

Artistry of Wine Co-Chairs and Foundation Fighting Blindness National Trustees Joel and Barbara Stone of Highland Park have two sons affected with Retinitis Pigmentosa. When our first son, Michael, was diagnosed we were told there is no treatment or cure for his degenerating retinal disease, says Barbara. Today there is still no cure, but thanks to the promising research funded by the Foundation Fighting Blindness, there is hope for a brighter future for all those affected with these blinding diseases.

Featured tasting stations at the event were: Bella Via, Bent Fork Bakery, Coopers Hawk Winery & Restaurant, Copper Fiddle Distillery, Half Day Brewing Company, Highland Park Country Club, KOVAL Distillery, La Macchina Caf, Maggianos Little Italy, Onion Garden, Park Street, Uncle Julios, Pinstripes, Revolution Brewery, Spin-Spun All Natural Confections.

Submitted by Foundation Fighting Blindness The Foundation Fighting Blindness is a national non-profit organization driving the research that will lead to preventions, treatments and cures for retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases that affect more than 10 million Americans. Since 1971, the Foundation has raised nearly $700 million as the leading non-governmental funder of inherited retinal research. Breakthrough Foundation-funded studies using gene therapy have restored significant vision in children and young adults who were previously blind, paving the way for additional clinical trials to treat a variety of retinal diseases. The Foundation also has nearly 45 chapters that provide support, information and resources to affected individuals and their families in communities across the country.

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Artistry of Wine – Daily North Shore

NightstaRx Raises $45M to Fund Phase III Study with Retinal … – Genetic Engineering & Biotechnology News (blog)

U.K. firm NightstaRx raised $45 million in a Series C financing round to support continued clinical development of its pipeline of retinal gene therapies, including a pending Phase III study with lead candidate NSR-REP1 for treating choroideremia. The new funds will also be used to support an ongoing Phase I/II study with NSR-RPGR in patients with X-linked retinitis pigmentosa (RP), and a proposed Phase I/II trial with a gene therapy product targeting an inherited form of macular dystrophy. Nightstar projects starting the macular dystrophy clinical trial during late 2018.

Investors in the Series C round included Nightstars existing investors Syncona and New Enterprise Associates (NEA) and new investors Wellington Management Company and Redmile Group. As an original investor in Nightstar, our goal from day one was to build a global gene therapy leader with the capability of developing multiple programs for inherited retinal diseases, commented Chris Hollowood, Ph.D., chairman of the board of Nightstar and chief investment officer of Syncona, which is funded by The Wellcome Trust. We welcome Wellington Management and Redmile Group as investors and look forward to working with them and NEA to fulfill Nightstars potential.

Founded in 2014 by researchers at the University of Oxford, Nightstar is developing a pipeline of one-time potentially curative treatments for rare inherited retinal diseases. Lead candidate NSR-REP1 is an adeno-associated virus (AAV) vector-based gene therapy in development for treating choroideremia, a rare X-linked inherited retinal dystrophy for which there are currently no disease-modifying therapies. The AAV vector is administered by injection under the retina, using standard surgical procedures performed under local anesthetic. Nightstar says a Phase I/II study carried out by the University of Oxford confirmed long-term benefits of the treatment including vision improvement or stabilization.

The firms AAV-vector-based NSR-RPGR gene therapy for X-linked RP is designed to deliver a normal copy of the RP GTPase regulator (RPGR) gene, which Nightstar says is mutated in more than 70% of cases of X-linked RP. The procedure similarly involves injecting the gene-carrying vector under the retina. The ongoing Phase I/II study with NSR-RPGR was started in March.

Nightstar has ongoing collaborations with the University of Oxford, the Bascom Palmer Eye Institute, and the Institute for Ophthalmic Research, Tbingen University Hospital. In February, the firm inked a collaboration with Netherlands-based Preceyes to develop a subretinal drug delivery technology based on the latters high-precision robotic device for ocular surgery.

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NightstaRx Raises $45M to Fund Phase III Study with Retinal … – Genetic Engineering & Biotechnology News (blog)

7th International Conference and Exhibition on Cell and Gene Therapy – Technology Networks

Conference Series LLC welcomes you to attend the 7th International Conference and Exhibition on Cell & Gene Therapy during March 15-17, 2018 at London, UK. We cordially invite all the participants who are interested in sharing their knowledge and research in the arena of Cell & Gene Therapy.

Cell and Gene Therapy Conference is to ameliorate the knowledge, awareness, and education on cell and gene therapy leading to the discovery of genetic and cellular therapies which aid to alleviate the human disease as it is the most significant emerging technology in the eyes of Medical, Biotechnology, Pharmaceuticals and Academia. Cell and Gene Therapy Conference 2018 is an excellent opportunity for the delegates from Universities and Institutes to interact with the world class Scientists.

Cell Therapy Conferences will provide a perfect platform to all the Doctors, Researchers Business Delegates and Scientists to approach and deliver all the attendees about the latest scientific advancements on the respective sphere.

Gene Therapy Conferences strategic astuteness is to be an event for bringing together Scientists, Physicians, International mix of leading Universities, Cell Gene Therapy Institutions to transform the practice of medicine by incorporating the use of genetic and cellular therapies to control and cure human disease.

This three-day Gene Therapy Event will address key issues concerning cell and gene therapy in the broader context of cellular and genetic disorder. Organized around daily themes, the Conference focuses on moving from present knowledge to future solutions

For more details:


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Their children are dying. So these families are racing to raise money for research no one else will fund – STAT

Taylor Sabky spent this past Mothers Day in shock, absorbing the news that her toddler, Purnell, was dying. Hed been diagnosed days before with Niemann-Pick type A an ultra-rare genetic disease that typically kills children by age 3. It was inconceivable.

When wed look at him, he was smiling. He has such a sweet personality, she said. Its been really tough to imagine hes dying.

So she and her husband, Sam, made a vow:save Purnell.


Thats the tagline of the couples wildly successful crowdfunding campaign, which has raised more than $600,000 in just over a month. The aim? To speed development of a one-shot experimental gene therapy that might, perhaps, treat their sons deadly neurodegenerative disease.

Rare diseases are increasingly attractive to biopharma companies, which can charge premium prices if they come up with a therapy. (One drug that just hit the market is priced at$750,000 for the first year of treatment.) But before theyll invest heavily in a field, companies want to see compelling early-stage science.

So families like the Sabkys are turning to the internet to raise money from friends and from total strangers to fund basic research at universities and hospitals.

A treatment for Zoe: Inside the race to build a therapy for a devastating rare disease

It seems the rare disease space is a lucrative, pretty sexy space for companies. But theres still too much risk, in our opinion, for a company to just jump in, said Steven Laffoon, who runs the Wylder Nation Foundation, a nonprofit that focuses on spurring research into Niemann-Pick.

The foundation is helping families like the Sabkys fundraise and funnel money to researchers, in hopes that theyll be able to push the science to a point where we can maybe spark some industry interest to take that path to the finish line, Laffoon said.

It doesnt take huge sums to make a dent: Just $100,000, given to the right lab, can go a long way toward developing a novel compound or screening the existing library of drugs for one that might be useful against a particular rare disease, said Arvin Gouw, vice president of research at the nonprofit Rare Genomics Institute.

The key thing about the families is, they can give you funds early, before [the National Institutes of Health] would be ready to give you that additional funding, saidDr. Elliott Sherr, a pediatric neurologist at the University of California, San Francisco. Some of his research into a rare genetic disorder was subsidized by patients crowdfunding campaigns.

Even better than the funds, he said, is the awareness that comes when a patients family goes public with pleas for research. In just two years, family activism helped bring forward more than 60 patients with the rare genetic mutation he studies, known as DDX3X. Having such a large pool of patients available to participate in trials accelerates the research process, he said and thats a big deal for a disorder that was essentially undiscovered just two years ago.

No matter how much they raise, however, the families know they must always temper their expectations.

Its a long and often heartbreaking path from early glimmers of hope in a lab to actual therapies that help patients in the clinic. Many drugs that show promise in rodents fizzle when tested in humans. And though rare disease treatments typically get speedier review at the Food and Drug Administration, it can still take years to get a product from lab to market.

So for all these families, its a long shot that theyll be able to save their own children.

The hope, of course, is that some other child might benefit where theirs did not.

As an infant, Purnell Sabky was slow to hit developmental milestones. His parents didnt think much of it. But at Purnells 6-month checkup, his pediatrician noticed that his liver was enlarged leading them to the doorstep of the Boston Childrens Hospital genetics department.

After a battery of tests, they got a diagnosis: Niemann-Pick type A, a disease with zero options for treatment.

We left with a death sentence, basically: Go home and love your kid, said Taylor Sabky, who is 29 and teaches math to immigrant students in the Boston area. Sam Sabky, also 29, runs a gourmet coffee startup called Kings Row Coffee. The two met as undergrads at Princeton University; Purnell is their first child.

We left with a death sentence, basically.

Niemann-Pick belongs to a family of rare diseases called lysosomal storage disorders. A mutation in the SMPD1 gene leads to a dearth of an enzyme, sphingomyelinase, which in turn leads to a buildup of a type of fat called sphingomyelin. This overload of bad fats winds up killing cells, particularly in the brain, lungs, spleen, and liver.

There are four types of the disease: type A, B, C1, and C2. Purnells variety, type A, is as rare as it gets, Sam Sabky explained and by far the worst.

As the family processed that horrifying news, they also started to dig deeper into the science behind the disease.

We found out that there was research for this gene therapy treatment, and it was closer than we thought. The barrier was just funding, Taylor said. That turned a hopeless situation into a hopeful one.

My daughter is fighting a rare disease. A streamlined FDA wont help her

With the help of the Wylder Nation Foundation, the Sabkys quickly learned that researchers at the University of California, San Francisco, had developed a virus containing a gene that could correct the enzyme deficiency in patients with Niemann-Pick type A.

But its costly and time-consuming to multiply that virus enough times to make an impact when its injected into a patient.

The research team needed about half a million dollars to take that next step. So the Sabkys made a moving video showing Purnell, whos now 14 months old, laughing in his high chair and cuddling with his mom and dad. They posted it on the crowdfunding site GoFundMe, set a goal of raising $750,000 by the end of June, and worked with a public relations firm to pitch their story to local and national media.

It worked: In the past month, news outlets ranging from Boston television news stations to People magazine have covered Purnells story.

Weve definitely taken a business approach here. Sam and Taylor have been very strategic, for instance, in how and when they put out social media posts about Purnell, said Laffoon, Wylder Nations founder. And all kinds of wonderful people have come out of the woodwork to help.

All kinds of wonderful people have come out of the woodwork to help.

Steven Laffoon, founder of Wylder Nation Foundation

The first donations came in within hours. So far, the Sabkys have collected more than 8,000 pledges, many of them anonymous, in amounts ranging from $10 to $10,000.

Among the most touching contributions have been small donations from the children Taylor Sabky teaches. One student, who lives in a homeless shelter, gave $10 to the cause and said she was sorry she couldnt give more. Taylor Sabkys desk is filled with posters and inspirational letters from people who want to help save her son.

About $500,000 of the money raised by the Sabkys will fund research at Childrens Hospital of Philadelphia to create the viral vector that could deliver the gene therapy to patients.

Thats projected to take about six months an eternity when dealing with a fast-moving neurodegenerative disease like Purnells. But the vector isnt meant exclusively for Purnell: Theyre looking to manufacture enough for a full Phase 1/2 trial that could enroll six to eight patients.

In the meantime, theres a ton of red tape to sift through: The Sabky family needs to get permission from the FDA to allow Purnell to take part in this experimental gene therapy. The researchers, too, need regulatory approval to run the clinical trial. Some of the crowdfunded money will be used to prepare those applications.

This toddler with a rare disease got a life-changing treatment. Why cant all kids?

The family will also likely appeal to the FDA to allow Purnell to take a drug from Genzyme that was developed for a different form of the disease, Niemann-Pick type B. The Sabkys hope to slow the course of Purnells disease with whats essentially an off-label therapy.

Its nice to know that there are steps we can take: Were not just winging it, Sam Sabky said. Right now, theres a chance everything will line up. Its not a great chance, but a chance so we have to take it.

One of the most successful crowdfunding campaigns for rare disease was led in recent years by the parents of Eliza ONeill.

They raised more than $4 million to speed up research for Sanfilippo syndrome, another lysosomal storage disorder, with about $2 million coming directly from a crowdfunding campaign. This helped Eliza, who has the disease, get access last May to an experimental gene therapy from Cleveland biotech Abeona Therapeutics. The trial is very small, and results are preliminary, but patients so far seem to be responding.

Then there are Leena and Anil Panwala, who have raised more than $150,000 to support research for their daughter, Ariya, whowas diagnosed last year with a genetic disease called infantile neuroaxonal dystrophy, or INAD.They dont want to leave it up to the whims of pharmaceutical companies or federal grant reviewers to determine which research gets funded.

Thats our biggest motivation for starting our foundation and raising the money: Were making sure the control comes from families affected by INAD, Leena said. It allows us to get more and more scientists researching this particular mutation and get more accountability from the researchers.

Right now, theres a chance everything will line up. Its not a great chance, but a chance so we have to take it.

Unlike the Sabkys, the Panwalas arent focusing on pushing forward a single avenue of research. A gene therapy has potential, but Leena Panwala has seen this treatment method fail in patients.That opened our eyes to not put our eggs in one basket, she said.

So one of the Panwalas initial aims is to create a postdoctoral position focused exclusively on the disease at a university where research for an INAD gene therapy is already underway. Next year, theyll also sponsor a $100,000 research grant through the Rare Genome Institute.

The family plans to continue to raise money in their daughters name. Theyll fund enzyme replacement therapy, research into supplements, further study of existing drugs anything that might give Ariya a chance.

The Sabkys know that gene therapies for lysosmal storage disease will be far more effective the earlier theyre administered before the lipids have had too much time to accumulate in the body.

By the time the treatment is ready to test, Purnells disease may have already progressed too far for him to benefit. The Sabkys know that. But they keep pushing.

We know there will be a point where hes too far gone neurologically for the treatment to work, Sam Sabky said. Gradually hell become distant, and lose his smile and laugh. Thats really the saddest part were racing against.

Meghana Keshavan can be reached at Follow Meghana on Twitter @megkesh


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Their children are dying. So these families are racing to raise money for research no one else will fund – STAT

New technique enables safer gene-editing therapy using CRISPR – Phys.Org

June 29, 2017 A CRISPR protein targets specific sections of DNA and cuts them. Scientists have turned this natural defense mechanism in bacteria into a tool for gene editing. Credit: Jenna Luecke and David Steadman/Univ. of Texas at Austin

Scientists from The University of Texas at Austin took an important step toward safer gene-editing cures for life-threatening disorders, from cancer to HIV to Huntington’s disease, by developing a technique that can spot editing mistakes a popular tool known as CRISPR makes to an individual’s genome. The research appears today in the journal Cell.

Scientists already use the gene-editing tool called CRISPR to edit the genetic code of nearly any organism. CRISPR-based gene editing will have an enormous impact on human health. More than a dozen clinical trials employing CRISPR on human cells are reportedly already underway, but the approach is imperfect. In theory, gene-editing should work much like fixing a recurring typo in a document with an auto-correct feature, but CRISPR moleculesproteins that find and edit genessometimes target the wrong genes, acting more like an auto-correct feature that turns correctly spelled words into typos. Editing the wrong gene could create new problems, such as causing healthy cells to become cancerous.

The UT Austin team developed a way to rapidly test a CRISPR molecule across a person’s entire genome to foresee other DNA segments it might interact with besides its target. This new method, they say, represents a significant step toward helping doctors tailor gene therapies to individual patients, ensuring safety and effectiveness.

“You and I differ in about 1 million spots in our genetic code,” says Ilya Finkelstein, an assistant professor in the Department of Molecular Biosciences at UT Austin and the project’s principal investigator. “Because of this genetic diversity, human gene editing will always be a custom-tailored therapy.”

The researchers took a DIY approach to developing the equipment and software for their technique, using existing laboratory technology to develop CHAMP, or Chip Hybridized Affinity Mapping Platform. The heart of the test is a standard next generation genome sequencing chip already widely used in research and medicine. Two other key elementsdesigns for a 3-D printed mount that holds the chip under a microscope and software the team developed for analyzing the resultsare open source. As a result, other researchers can easily replicate the technique in experiments involving CRISPR.

“If we’re going to use CRISPR to improve peoples’ health, we need to make sure we minimize collateral damage, and this work shows a way to do that,” says Stephen Jones, a postdoctoral researcher at UT Austin and one of three co-lead authors of the paper.

Andy Ellington, a professor in the Department of Molecular Biosciences and vice president for research of the Applied Research Laboratories at UT Austin, is a co-author of the paper. He says this method also illustrates the unpredictable side benefits of new technologies.

“Next generation genome sequencing was invented to read genomes, but here we’ve turned the technology on its head to allow us to characterize how CRISPR interacts with genomes,” says Ellington. “Inventive folks like Ilya take new technologies and extend them into new realms.”

This work can also help researchers predict which DNA segments a certain CRISPR molecule will interact with even before testing it on an actual genome. That’s because they’re uncovering the underlying rules that CRISPR molecules use to choose their targets. For example, they found that the CRISPR molecule they tested, called Cascade, pays less attention to every third letter in a DNA sequence than to the others.

“So if it were looking for the word ‘shirt’ and instead found the word ‘short,’ it might be fine with that,” says Jones.

That sounds counterintuitive, but can be really useful. CRISPR originated from a natural defense in bacteria used to guard against invading viruses that evolve rapidly. A good defense sees through slight changes in the viral genetic code.

Knowing these rules will lead to better computer models for predicting which DNA segments a specific CRISPR molecule is likely to interact with. And that can save time and money in developing personalized gene therapies.

Explore further: Modifying fat content in soybean oil with the molecular scissors Cpf1

More information: Cell (2017). DOI: 10.1016/j.cell.2017.05.044 ,

Journal reference: Cell

Provided by: University of Texas at Austin

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New technique enables safer gene-editing therapy using CRISPR – Phys.Org

Lowell biotech company Alcyone announces research deal with Pfizer – Lowell Sun

LOWELL — Alcyone Lifesciences, a small biotechnology company operating out of Mill No. 5, will partner with pharmaceutical giant Pfizer to study a new method of treating neurological disorders such as ALS, Alcyone’s chief executive said Thursday.

Alcyone CEO PJ Anand said his company had finalized a deal with Pfizer to begin a roughly eight-month research program using a Pfizer molecule and Alcyone technology in August. No financial terms of the agreement were disclosed.

“We’re pretty excited about this deal we did with Pfizer,” Anand said in an interview. “It’s a significant investment in disease-modifying therapies. It’s going to the root cause of the disease and treating that.”

A representative from Pfizer could not be reached for immediate comment Thursday.

The pre-clinical feasibility study will use a molecule developed by Pfizer that could theoretically correct genetic mutations behind several debilitating neurological disorders. However, Anand said it can be challenging to get the treatment into position with more conventional techniques.

That’s where Alcyone comes in: the research will use Alcyone’s “Pulsar platform,” a technique the company developed to transport molecules directly to the brain, alongside Pfizer’s treatment. Anand likened it to Pfizer providing a package and Alcyone providing an instant-delivery drone that could drop the package off right on a doorstep.

“You need something advanced as well as precise because you don’t want to contaminate the good parts of the brain,” he said.

The process is a form of gene therapy, an emerging and experimental way of treatment that attempts to bring relief or even a cure by altering DNA itself to fix mutations that cause disorders. Alcyone and Pfizer’s partnership will use the technique to examine the feasibility of treating neurological disorders including ALS and congenital childhood seizures.

“What happens here is a one-time shot that you go and make the patient feel substantially better or cure the patient,” Anand said.

Alcyone was founded in 2010 and operated in Concord and Ayer before moving to Lowell’s Boott Mills complex in 2014. The company did not receive funding from the city or UMass Lowell, but it did win a $750,000 loan from the Massachusetts Life Science Center’s Accelerator Program.

Anand expressed hope that the study with Pfizer — as well as an earlier, separate deal to research technology to treat brain cancer — would create new opportunities for growth for the company, which currently employs nine people.

Operating out of the Mill No. 5 building, Alcyone is part of the Hamilton Canal Innovation District that has experienced some struggles in finding momentum. Last week, city officials invited developers and real-estate leaders to the district for a presentation on the opportunities available.

Anand said he hopes city officials will also make “concerted efforts” to promote biotechnology breakthroughs taking place in the Mill City and to attract new investments in the area.

“This could be a wonderful spot for that,” he said. “It would be great to see the city push that.”

If his company expanded, Anand said he hopes to stay in Lowell, but that a lack of accessible parking today could pose a challenge. A 900-spot parking garage in the HCID is being designed, and city officials hope that will relieve some pressure.”

“(Parking) is not just expensive, but it’s unreliable, and I think it’s disruptive,” Anand said. “Parking is going to be the biggest issue to me.”

Follow Chris on Twitter @ChrisLisinski

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Lowell biotech company Alcyone announces research deal with Pfizer – Lowell Sun

Massachusetts girl may be among first-ever to receive gene therapy for rare disease after parents push for cure – Fox News

An 11-year-old girl in Massachusetts is at the forefront of a disease so rare, that it is believed only 22 people worldwide have been diagnosed with it. Talia Duff, who was born with Down syndrome and later diagnosed with Charcot-Marie-Tooth Neuropathy Type 4J (CMT4J), is slated to be among the first to enroll in a clinical trial that is awaiting FDA approval after her parents refused to watch her fall victim to the degenerative genetic disease.

Its a horrible feeling to go to a doctor and be told that theres nothing that can be done that the best you can do is try to make your child comfortable and enjoy the time you have together, John Duff, Talias dad, told PEOPLE. I learned to cherish moments in life that I would otherwise take for granted.


The Duff family, which includes mom Jocelyn and older sister Teaghan, had noticed Talia struggling to crawl at around age four, and a regression in a number of other motor skills that at the time was attributed to her Down syndrome, and later to Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). Subsequent failed therapies and a diagnoses of osteoporosis due to prescribed steroids caused her parents to push for another diagnosis at Boston Childrens Hospital, according to a post on the familys Cure CMT4J Foundation website.

We learned that Talia did not in fact have CIDP but instead had an extremely rare form of Charcot Marie Tooth Disease a degenerative, genetic disease called CMT4J, the post read.


The family learned the disease would slowly take over Talias body like a form of amyotrophic lateral sclerosis (ALS), eventually causing paralysis and robbing her of her ability to breathe. In the two years since her diagnosis, Talia lost her ability walk or even raise her arms.

We were supposed to sit back and watch our child live her life in reverse, the post on Cure CMT4J Foundation read. I decided not to accept this. I stayed up late nights pouring over scientific papers and booked appointments with the top CMT doctors in the world. We traveled to the University of Iowa and then Vanderbilt University, where we met Dr. Jun Li.


It was at the meeting with Li that the Duffs learned of a genetic therapy that could potentially cure Talias disease, but that it was eight-to-ten years away from production. Knowing that time was of the essence for Talia, Jocelyn began connecting with other parent advocates and the family started the Cure CMT4J Foundation with a goal of raising $1 million for research. She met with a team of eight researchers in Maryland, who concluded that the gene therapy would have a lasting effect on Talia, and they are now working to attain proof of concept approval from the FDA, PEOPLE reported.

With approval expected to come later this summer, Jocelyn is prepared to then push for approval of a human clinical trial, with Talia expected to be among the first to receive the gene therapy intravenously.

We feel hope now, Jocelyn told PEOPLE. People have said to me, This is a lot of work for you, and my response is, Hey, you would do this for your child, too. I simply cant stand by and do nothing.

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Massachusetts girl may be among first-ever to receive gene therapy for rare disease after parents push for cure – Fox News

Massachusetts Mom Convinces Scientists to Find Potential Cure for Daughter’s Rare Disease: ‘Anything Is Possible’ –

Shortly before Talia Duff of Ipswich, Massachusetts, turned 9, her mother noticed that she was losing mobility. Talia, who has Down syndrome, could no longer use a spoon or give a hug and her arms and legs had become increasingly weak.

Jocelyn Duff, a physicians assistant, and her husband, John Duff, dean at a community college, took their daughter to the hospital for testing and received devastating news in September 2015: Talia had a rare genetic disease called Charcot-Marie-Tooth Neuropathy Type 4J a disorder estimated to be shared by only 22 people worldwide. The disease causes profound muscle weakness and eventually affects the capability to breathe.

It was heartbreaking we were told there was no hope, no treatment, no cure, Jocelyn, 50, tells PEOPLE. There wasnt much research available about it, and that kept me awake at night. I wanted to do as much as I could.

Adds John, Its a horrible feeling to go to a doctor and be told that theres nothing that can be done that the best you can do is try and make your child comfortable and enjoy the time you have together. I learned to cherish moments in life that I would otherwise take for granted.

The Duffs soon realized that to save Talias life, they would have to take the search for a cure into their own hands. They created the Cure CMT4J Foundationto raise money for research, and Jocelyn gleaned through every story she could find on the Internet in search of researchers and scientists who knew something about the disease.

When Dr. Jun Li, director of the CBT clinic at Vanderbilt University, told her that gene therapy might help Talia, Jocelyn took her quest one step further: Last September, she asked all of the experts she had found in an online search if they would meet her in Bethesda, Maryland, to discuss working on a cure for CMT4J. Eight researchers showed up, each agreeing to work together to find a way to help Talia Duff.

It was an incredible moment hands started going up and people were saying, Lets get to work, Jocelyn recalls. It was so heartwarming and comforting I felt like I was walking on clouds for days.

Since that meeting, the Duffs have received some uplifting news: The research team concluded that gene therapy would have positive and lasting effects for Talia, who is now 11. Once FDA approval has been granted to begin the first clinical trial (hopefully by summers end, says Jocelyn), the Ipswich fifth-grader will be able to receive gene therapy intravenously.

We feel hope now, Jocelyn tells PEOPLE. People have said to me, This is a lot of work for you, and my response is, Hey, you would do this for your child, too. I simply cant stand by and do nothing.

Community efforts to fund research for the cure have thus far brought in more than $235,000 on the Duffs website,with a goal of reaching $1 million by the end of the year.

Talia has faced such tough monumental challenges, and yet, she smiles through it all and has never complained, says Marcia Gray, a family friend who helped organize several Duff Enough fundraisers. Its important to everyone, especially Talias school friends, to do what they can.

Once an active girl who enjoyed dance classes and riding her bicycle, Talia is now too weak to walk or lift up her arms. But her family is hopeful that if gene therapy stops the diseases progress, her peripheral nerves will heal, allowing her to get back some of her strength.

The lessons we learn and the technology we develop through helping families like the Duffs will ultimately help us create best practices and treatment for a wide variety of diseases, says Cathleen Lutz, senior director of the Rare and Orphan Disease Center at the Jackson Laboratory.Every person with a genetic health condition deserves the chance to lead a healthy, happy life.

The Duffs, who have another daughter, Teaghan, 14, know that time is their enemy, but they remain hopeful that the voluntary hard work of Talias research team will soon add years to her life.

Im floored by how far weve come in a year, John tells PEOPLE. To think that a little over a year ago, we were flying around the country, looking for a sliver of hope, and now were working on a cure. We realize that this is science and there is still a lot that can happen, but to get this far in that short amount of time is breathtaking.

Adds Jocelyn, Were so overwhelmed with gratitude for everyone who has gotten us this far. And now Talia is giving other families hope. To every family out there in a similar fight, we want to say, Dont give up. Anything is possible.

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Massachusetts Mom Convinces Scientists to Find Potential Cure for Daughter’s Rare Disease: ‘Anything Is Possible’ –

Arix leads $45M series B for gene therapy biotech LogicBio – FierceBiotech

LogicBio Therapeutics has got off a $45 million series B funding round as it eyes the cash for disease-modifying gene therapies in rare childhood diseases.

London-based investment firm Arix Bioscience led the oversubscribed round in the semi-stealth biotech, with new investors OrbiMed, Edmond De Rothschild Investment Partners, Pontifax, and SBI, along with previous investors OrbiMed Israel Partners, also stumping up cash.

Arix Bioscience’s investment manager, Daniel OConnell, M.D., Ph.D, will join Cambridge, Massachusetts-based LogicBios board as part of the raise. This brings its total raised to $50 million, much of which will be put toward finishing off preclinical work and moving them into human tests.

The biotech sets itself up as a breakthrough gene therapy company targeting lifelong cures for serious, early-onset rare diseases by combining the best of gene therapy and gene editing in a one-time treatment.

It was founded in 2014 with platform technologies discovered by Adi Barzel, Tel Aviv University, Dr Leszek Lisowski, Childrens Medical Research Institute, Australia, and Professor Mark Kay at Stanford University School of Medicine.

The first platform, GeneRide, is a technology that uses homologous recombination that is designed to allow site-specific transfer of therapeutic genetic material without the use of promoters or nucleases. The company says it also has access to a library of synthetic, non-pathogenic, recombinant adeno-associated viral (rAAV) vectors developed at Stanford that allows for better predictability of vector performance in clinical trials.

Joe Anderson, CEO of Arix Bioscience, said: Early intervention for rare genetic disorders in children is important and LogicBio is uniquely positioned at the forefront of this research area with its proprietary genetic therapy technology to deliver a durable cure for young patients with life-threatening genetic diseases and otherwise limited options. LogicBio has huge potential and, alongside its excellent team and investors, we look forward to supporting the company to achieve continued success in this area.

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Arix leads $45M series B for gene therapy biotech LogicBio – FierceBiotech

Biotech Gene Therapy names Juno, Kite, and Bluebird Bio still have room to run – Seeking Alpha

Author’s note: The following consists of excerpts from my 45-page May 30 report on bluebird bio (NASDAQ:BLUE), Kite Pharma (NASDAQ:KITE), and Juno Therapeutics (NASDAQ:JUNO). The focus in this submission is BLUE. Please check out my Seeking Alpha profile for important information. Global Gene Therapy Market

The gene therapy market is gaining popularity in the global medical community. The advent of advanced techniques for gene transfer has enabled the use of gene therapy for various new applications. Although it is still at an infant stage, its promise has led to a range of bullish estimates. Market research firm BCC Research forecasts the global market for DNA vaccines to grow at a 54.8% CAGR to $2.7 bln by 2019, while two other observers — Roots Analysis and Research and Markets — predict the gene therapy market as a whole to reach ~$11 bln by 2025. Another report from market intelligence firm Transparency Market Research forecasts that the global stem cell market will grow at a CAGR of > 20% in the next few years and said there is a rich pipeline of more than 500 cell and gene therapy products, which will drive significant capacity as the pipeline matures and progresses to commercial supply.

Key factors driving market growth include demand for novel and efficient therapies to treat cancers and other indications with high unmet needs. Other market drivers include completion of the human genome project, rising incidence and prevalence of cancers and other critical diseases, and the prospective launch of gene therapies in major global markets.

Most gene therapy products are in the pre-clinical or clinical research stage. To-date, there are only five marketed drugs, namely Glybera, Neovasculogen, Gendicine, Rexin-G, and Oncorine. However, these products constitute very little revenue for the gene therapy market. Most revenue for the gene therapy market is generated from products used in clinical trials.

Need for gene therapy: It is estimated that, approximately 5% of the global population suffers from a rare disease and half of the global population affected by rare diseases are children, making rare disease treatment a concern for children across the globe. There are about 7,000 known rare diseases that comprise the most complex healthcare challenges for researchers and health professionals — with most being difficult to diagnose due heterogeneity in disease epidemiology.

Rare diseases that affect 200,000 people in the US (as per the FDA definition) and a similar percentage in Europe are typically genetic in nature, and thus present a significant unmet need for potential regimes in the market.

As per World Health Organization, 80% of rare diseases are caused due to genetic abnormality and are inherited for generations. Approximately 5% of the rare diseases have a treatment and most of the current therapeutic approaches include gene therapy and cell therapy. A significant gap between demand and supply of rare disease drugs is expected to create a massive opportunity for manufacturers and researchers in the area of rare disease treatment.

How Does Gene Therapy Work?

Advances in biotechnology have brought gene therapy to the forefront of medical research. The prelude to successful gene therapy, the efficient transfer and expression of a variety of human gene into target cells, has already been accomplished in several systems.

Gene therapy may be defined as the introduction of genetic material into defective cells for a therapeutic purpose. While gene therapy holds great potential as an effective means for selective targeting and treatment of disease, the field has seen relatively slow progress in the development of effective clinical protocols. Although identifying genetic factors that cause a physiological defect is straightforward, successful targeted correction techniques are proving continually elusive. Hence, safe methods have been devised to do this (using several viral and no-viral vectors). Two main approaches have emerged in-vivo modification and ex-vivo modification. Retrovirus, adenovirus, adeno-associated virus are suitable for gene therapeutic approaches; these are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and large capacity for therapeutic DNA.

Viral Vectors: These are virus-based vectors. Examples include retrovirus vector, adeno virus vector system, adeno associated virus vector, and herpes simplex virus. Extensive research is being conducted on the various viral vectors used in gene delivery. Non-viral Vectors: Examples of non-viral vector systems include pure DNA constructs, lipoplexes, DNA molecular conjugates, and human artificial chromosomes. Owing to the following advantages, non-viral vectors have gained significant importance in the past few years as they are less immune-toxic; there is risk-free repeat administration; and relative ease of large-scale production.

A major disadvantage is that the corrected gene needs to be unloaded into the target cell, and the vector has to be made to reach the required treatment site.

Gene therapy has transitioned from the conceptual, technology-driven, laboratory research, to clinical trial stages for a wide variety of diseases. In addition to curing genetic disorders such as Hemophilia, Chronic Granulomatous Disorder, and Severe Combined Immune Deficiency (ADA-SCID), it is also being tested to cure acquired diseases such as cancer, neurodegenerative diseases, influenza, and hepatitis.

Gene therapy is not limited to any particular disease. It is proving to be a promising treatment for rare diseases such as X-linked adrenoleukodystrophy. The therapy has proved effective in research conducted for the following diseases:

Fat Metabolism Disorder: Gene therapy is used to correct rare genetic diseases caused due to lipoprotein lipase deficiency. This deficiency leads to fat molecules clogging the blood stream. An adeno-associated virus vector is used to deliver the corrected copy of the LPL to the muscle cells. This corrected copy prevents excess accumulation of fat in the blood by breaking down the fat molecules. In 2012, the EU approved Glybera, the first viral gene therapy treatment for LPLD, manufactured by UniQure. Glybera is likely to be approved for the American market by 2018.

Adenosine Deaminase Deficiency: Gene therapy has successfully been used to treat another inherited immune disorder — ADA deficiency. More importantly, none of the patients undergoing this treatment developed any other disorder. The retroviral vector is used in multiple small trials to deliver the functional copy of the ADA gene. Primarily, all the patients involved in these trials did not require any injection of ADA enzyme as their immune functions had immensely improved.

Severe Combined Immune Deficiency: A lot of documented work is already available regarding treating this immunodeficiency with gene therapy; however, clinical trials have not shown promising results. The viral vectors used during the trials triggered leukemia in patients. Since then, focus of the research and trials has been on preparing new vectors that are safe and do not cause cancer.

Hemophilia: Patients with hemophilia suffer excessive blood loss as the blood clotting protein (Factor IX) is absent. Researchers have successfully inserted the missing gene in the liver cells using an adeno-associated viral vector. After undergoing this treatment, patients experienced less bleeding as their body was able to create some of the Factor IX protein.

Cystic Fibrosis (CF): CF is a chronic lung disease caused due to a faulty CFTR gene. Genes are injected into cells using a virus. Recent studies also include testing the cationic liposome (a fatty container) to deliver DNA to the faulty CFTR gene, thus making the use of the non-viral gene carrier more successful. Phase II trials using this therapy were published in early 2015, which promised a novel therapeutic approach to CF.

-thalassemia: Clinical trials on gene therapy for -thalassemia (the faulty beta-globin gene, which codes for an oxygen-carrying protein in (RBC) can be tracked back to 2007. Blood stem cells were taken from the patients bone marrow and a retrovirus was used to transfer a working copy of the faulty gene. The modified stem cells were re-injected into the body to supply functional red blood cells. This treatment, once conducted, lasted over seven years, with the patient not undergoing blood transfusion during this time.

Hereditary Blindness: Currently, gene therapy is being tested to treat degenerative form of inherited blindness, where patients lose light-sensing cells in their eyes over time. Experimental data suggests that the animal models of a mouse, rat, and dog show slow or even reverse vision loss using gene therapy. The most important advantage associated with gene therapy for eye disorders is that AAV (adeno-associated virus) cannot shift from the eye to other body parts, and hence does not cause an immune reaction.

Parkinson’s Disease: Patients with Parkinson’s disease lose the ability to control their movement as their brain cells stop producing the dopamine molecule used for signaling. A small group of patients showed improved muscle control when a small area of their brain was treated with a retroviral vector that contained dopamine-producing genes.

This is because cancer genetics is a novel treatment method, marked by high R&D costs. The therapy targets diseases with high unmet needs; this has been the driving force behind academic research laboratories, small biotech firms, and large pharmaceutical companies. The therapy is of short-duration treatment or mostly one-time treatment customized to individuals, and often in small patient populations.

bluebird bio (BLUE) is a clinical-stage biotechnology company that focuses on developing transformative gene therapies for severe genetic diseases and cancer. Its product candidates include Lenti-D, which is in phase II/III clinical studies for the treatment of cerebral adrenoleukodystrophy — a rare hereditary neurological disorder — and LentiGlobin, which is in four clinical studies for the treatment of transfusion-dependent beta-thalassemia and severe sickle cell disease. The companys lead product candidate is bb2121, a chimeric antigen receptor (CAR) T cell receptor (TCR) product candidate that is in phase I trial for the treatment of relapsed/refractory multiple myeloma.

The company’s gene therapy platform is based on viral vectors that utilize a non-replicating version of the Human Immunodeficiency Virus Type 1 (HIV-1). Its lentiviral vectors are used to introduce a functional copy of a gene to the patient’s own isolated hematopoietic stem cells (HSCs) in the case of its LentiGlobin and Lenti-D product candidates, or the patient’s own isolated white blood cells, which include T cells, in the case of its bb2121 product candidate.

BLUE has a strategic collaboration with Celgene Corporation (CELG) to discover, develop, and commercialize disease-altering gene therapies in oncology; with Kite Pharma (KITE) to develop and commercialize second generation T cell receptor product candidates against an antigen related to certain cancers associated with the human papilloma virus; and with Medigene (Germany) for the research and development of (TCR) product candidates directed against approximately four antigens for the treatment of cancer indications. Founded in 1992 and headquartered in Cambridge, Massachusetts, the company was formerly known as Genetix Pharmaceuticals and later changed its name to bluebird bio (Incorporated) in September 2010.

With its lentiviral-based gene therapies, T-cell immunotherapy expertise, and gene-editing capabilities, BLUE has built an integrated product platform with broad potential application for severe genetic diseases and cancer. BLUE’s approach to gene therapy is based on viral vectors that utilize the Human Immunodeficiency Virus Type 1 or HIV-1. The HIV-1 vector is stripped of all the components that allow it to self-replicate and infect additional cells. HIV-1 is part of the lentivirus family of viruses. The vectors are used to introduce a modified copy of a gene from the patients own blood stem cells called hematopoietic stem cells (HSC), which reside in the patient’s bone marrow. HSCs divide cells that allow for sustained expression of the modified gene.


bluebird is developing the Lenti-D product candidate to treat patients with cerebral adrenoleukodystrophy.

Adrenoleukodystrophy is a rare X-linked, metabolic disorder caused by mutations in the ABCD1 gene, which results in a deficiency in adrenoleukodystrophy protein, or ALDP, and subsequent accumulation of very long-chain fatty acids. Symptoms of CALD usually occur in early childhood and progress rapidly if untreated, leading to severe loss of neurological function and eventual death.

Completed non-interventional retrospective study (the ALD-101 Study)

CALD is a rare disease, and data on the natural history of the disease, as well as the efficacy and safety profile of allogeneic HSCT, is limited in scientific literature. To properly design clinical studies of Lenti-D and interpret the efficacy and safety results thereof, at the recommendation of the FDA, bluebird performed a non-interventional retrospective data collection study to assess the natural course of the disease in CALD patients that were left untreated in comparison with the efficacy and safety data obtained from patients that received allogeneic HSCT.

For this study, data was collected from four US sites and one French site on a total of 137 subjects, 72 of whom were untreated and 65 were treated with allogeneic HSCT.

Starbeam Study (ALD-102) Phase II/III clinical study in subjects with CALD

The company is currently conducting a phase II/III clinical study of Lenti-D product candidate in the US, referred to as the Starbeam Study (ALD-102), to examine the safety and efficacy of Lenti-D product candidate in subjects with CALD. The study was fully enrolled in May 2015; however, in December 2016, the company amended the protocol for this study to enroll up to an additional eight subjects in an effort to enable the first manufacture of Lenti-D product candidate in Europe and the subsequent treatment of subjects in Europe, and to bolster the overall clinical data package for potential future regulatory filings in the US and Europe. It intended to begin treating the additional patients in early 2017.

The ALD-103 (observational) study

bluebird is also conducting the ALD-103 study, an observational study of subjects with CALD treated by allogeneic HSCT. This study is ongoing and is designed to collect efficacy and safety outcomes data in subjects who have undergone allogeneic HSCT over a period that is contemporary with the Starbeam study.

Lentiglobin Product

Transfusion-dependent -thalassemia (TDT)

-thalassemia is a rare hereditary blood disorder caused by a mutation in the -globin gene, resulting in the production of defective red blood cells, or RBCs. Genetic mutations cause the absence or reduced production of beta chains of hemoglobin, or -globin, preventing the proper formation of hemoglobin A, which normally accounts for more than 95% of the hemoglobin in the blood of adults.

Limitations of current treatment options

In geographies where treatment is available, patients with TDT receive chronic blood transfusion regimens. These regimens consist of regular infusions with units of packed RBC, or pRBC, usually every three to five weeks, to maintain hemoglobin levels and control symptoms of the disease.

The only potentially curative therapy for -thalassemia today is allogeneic HSCT. However, complications of allogeneic HSCT include risk of engraftment failure in unrelated human-leukocyte-antigen, or HLA, matched patients, risk of life-threatening infection, and risk of GVHD — a common complication in which donor immune cells (white blood cells in the graft) recognize the cells of the recipient (the host) as foreign and attack them. As a result of these challenges, allogeneic HSCT can lead to significantly high mortality rates, particularly in patients treated with cells from a donor who is not a matched sibling, and in older patients. Overall, TDT remains a devastating disease, with an unmet medical need.

The Northstar Study (HGB-204) Phase I/II clinical study in subjects with TDT

The Northstar study is a single-dose, open-label, non-randomized, multi-site phase I/II clinical study in the US, Australia, and Thailand to evaluate the safety and efficacy of the LentiGlobin product candidate in increasing hemoglobin production and eliminating or reducing transfusion dependence following treatment. In March 2014, the first subject with TDT was treated in this study, and, in May 2016, the study was fully enrolled.

The study enrolled 18 adults and adolescents. To be eligible for enrollment, subjects had to be between 12 and 35 years of age, with a diagnosis of TDT, and received at least 100 mL/kg/year of pRBCs or more than or equal to eight transfusions of pRBCs per year in each of the two years preceding enrollment.

Efficacy will be evaluated primarily by the production of 2.0 g/dL of hemoglobin A containing A-T87Q-globin for the six-month period between 18 and 24 months, post transplants. Exploratory efficacy endpoints include RBC transfusion requirements (measured in milliliters per kilogram) per month and per year, post transplants.

The HGB-205 study Phase I/II clinical study in subjects with TDT or with severe SCD

bluebird is conducting the HGB-205 study, a phase I/II clinical study, in France to study the safety and efficacy of its LentiGlobin product candidate in the treatment of subjects with TDT and of subjects with severe SCD. In December 2013, the company said that the first subject with TDT had been treated in this study; in October 2014, bluebird declared that the first subject with severe SCD had been treated in this study. By February 2017, the study had been fully enrolled.

bluebird is conducting HGB-206 multi-site phase I clinical study in the US to evaluate the safety and efficacy of its LentiGlobin product candidate for the treatment of subjects with severe SCD. In October 2016, the company amended the protocol of its HGB-206 study to expand enrollment and incorporate several process changes, including updated drug product manufacturing process. Enrollment had begun under this amended protocol, and, in February 2017, the company treated the first subject under this amended protocol.

The Northstar-2 Study (HGB-207) Phase III study in subjects with TDT and a non-0/ 0 genotype

The Northstar-2 study is an ongoing single-dose, open-label, non-randomized, international, multi-site phase III clinical study to evaluate the safety and efficacy of the LentiGlobin product candidate to treat subjects with TDT and non-0/0 genotype. Approximately 23 subjects will be enrolled in the study, consisting of at least 15 adolescent and adult subjects between 12 and 50 years of age at enrollment, and at least 8 pediatric subjects less than 12 years of age at enrollment. In December 2016, the first subject had received treatment with the LentiGlobin product candidate.

The planned Northstar-3 Study (HGB-212) Phase III Study for TDT in subjects with TDT and a 0/ 0 genotype

The company plans the initiation of HGB-212, a phase III clinical study of LentiGlobin in patients with TDT and the 0/0 genotype in 2H FY2017.

bluebird expects to enroll up to 15 adult, adolescent, and pediatric subjects. The company anticipates that the primary endpoint of the Northstar-3 study will be transfusion reduction, which is defined as a demonstration of a reduction in the volume of pRBC transfusion requirements in the post-treatment time period of 12-24 months, compared with the average annual transfusion requirement in the 24 months prior to enrollment.

Sickle Cell Disease

SCD is an inherited disease that is caused by a mutation in the -globin gene; this results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life, and, sometimes, early death. Where adequate medical care is available, common treatments for patients with SCD largely revolves around the management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced therapy for SCD is allogeneic hematopoietic stem cell transplantation (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft-versus-host disease, and opportunistic infections — particularly in patients who undergo non-sibling-matched allogeneic HSCT.

In March 2017, bluebird announced the Publication of the Case Study on the First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine. Patient 1204, a male patient with S/S genotype, was enrolled in May 2014 at 13 years of age into the HGB-205 clinical study. The patient underwent a regular transfusion regimen for four years prior to this study. Over 15 months since transplant, no SCD-related clinical events or hospitalizations occurred — contrasting favorably with the period before the patient began regular transfusions. All medications were discontinued, including pain medication.

The successful outcome in Patient 1204 demonstrates the promise of treatment with LentiGlobin gene therapy in patients with severe SCD and serves as a guide to optimize outcomes in future patients.

Celgene Collaboration

In March 2013, BLUE entered into a strategic collaboration with Celgene to advance gene therapy in oncology (cancer), which was amended and restated in June 2015, and amended again in February 2016. The multi-year research and development collaboration focused on applying BLUEs expertise in gene therapy technology to CAR T cell-based therapies, to target and destroy cancer cells. The collaboration now focuses exclusively on anti- B-cell maturation antigen BCMA product candidates for a new three-year term.

Under the terms of the Amended Collaboration Agreement, for up to two product candidates selected for development under the collaboration, BLUE is responsible for conducting and funding all research and development activities performed up through completion of the initial phase I clinical study of such a product candidate.

In February 2016, Celgene exercised its option to obtain an exclusive worldwide license to develop and commercialize bb2121, the first product candidate under the Amended Collaboration Agreement, and paid the associated ($10 million) option fee. BLUE will share equally in all costs related to developing, commercializing, and manufacturing the product candidate within the US, if it elects to co-develop and co-promote bb2121 with Celgene. In case BLUE does not exercise its option to co-develop and co-promote bb2121, it will receive an additional fee (of $10 million).


All three names in my May 30, 2017 (45-page) report are from the same space and I highly recommend taking a look at the entire report before making an investment decision. It is available on request.

This industry is in its infancy — most trials are only in Phase I or Phase II. The companies do not have earnings yet and that makes them difficult to value today. In my opinion, the upside here is significant, but you may have to hold on to these names for a few years in order to realize that upside, because today an argument can be made that the stocks have gotten a little bit ahead of themselves.

I am keeping my Buy recommendation on Juno (unchanged) and I am keeping my Hold recommendation on Kite (unchanged). There are currently seven institutions (each) with stakes of at least 250 million dollars in BLUE. There are nine institutions (each) with stakes of at least 175 million dollars in KITE. With JUNO the institutional ownership is much lower — many institutions probably got shaken out following deaths on the Juno trials last year. In my opinion the market over-reacted to those deaths. In fact, the shares have already bounced significantly since the low from last year following that market over-reaction (and insiders bought $500,000 worth of Juno shares recently).

I went in-and-out of KITE twice in the last couple of years and locked in gains of 35% both times. I most recently exited KITE at $87 a share on March 13.

The 52-week high on BLUE is $124 and the all-time high is $194.

There are 8,000,000 shares short and that is more than 10X the average daily volume.

My recommendation is to allocate 3% portfolio weight to this industry: 1.5% to BLUE, 0.75% to KITE, and 0.75% to JUNO.

I remember an analyst (many years ago) on CNBC defending his Sell recommendation on Amazon. It was trading at $100/share at the time. He defended the Sell rating by saying they lose money on every book they sell. AMZN recently hit $1,000 today. The lesson here is do not be afraid to invest in names with multi-billion market caps that are without EPS today. With KITE, BLUE and JUNO you must look out 3-5 years.


Why bluebird bio Stock Surged 20.7% Higher in January

Risks – Mayo Clinic

bluebird bio Reports First Quarter 2017 Financial Results and Recent Operational Progress

bluebird bio Announces Publication of Case Study on First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine

Annual Report 10K

Quarterly Report 10Q

Press Release | Investor Relations | Bluebird Bio

Kite Pharma (KITE) Posts Q1 Loss, Reveals CAR-T Patient Death

SHAREHOLDER ALERT: Bronstein, Gewirtz & Grossman, LLC Announces Investigation of Kite Pharma, Inc. (KITE)

KITE INVESTOR ALERT: Faruqi & Faruqi, LLP Encourages Investors Who Suffered Losses Exceeding $100,000 Investing In Kite Pharma, Inc. To Contact The Firm

SHAREHOLDER ALERT: Levi & Korsinsky, LLP Announces the Commencement of an Investigation Involving Possible Securities Fraud Violations by the Board of Directors of Kite Pharma, Inc.

Kite Investors See An Uncomfortable Parallel With Juno

Kite Pharma: History In The Making?

Kite Pharma: Still Time To Get In Ahead Of Lead Oncology Treatment Approval

Here’s What’s Dragging Kite Pharma Inc. Down Today — The Motley Fool

Global Gene Therapy Market to Reach US$316 Million by 2015, According to a New Report by Global Industry Analysts, Inc.

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapies Market will generate $204m in 2020

Cancer Gene Therapy Market size to exceed $4.3bn by 2024

Could gene therapy become biotech’s growth driver in 2017?

Cell Therapy 2016 – Year in Review (part 1)

Cancer Gene Therapy Market Size, Share, Industry Report 2024

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapy Clinical Trials Worldwide

Aranca Report – GENE THERAPY: Advanced Treatments for a New Era

International Journal Of Pharma Sciences and Research (IJPSR) – Gene therapy: Current status and future perspectives Gene Therapy Institute for Clinical and Economic Review

See the article here:
Biotech Gene Therapy names Juno, Kite, and Bluebird Bio still have room to run – Seeking Alpha

New research identifies key mechanism behind some deafness – Medical Xpress

June 29, 2017 Credit: CC0 Public Domain

Although the basic outlines of human hearing have been known for years – sensory cells in the inner ear turn sound waves into the electrical signals that the brain understands as sound – the molecular details have remained elusive.

Now, new research from the University of Maryland School of Medicine (UM SOM), has identified a crucial protein in this translation process.

The findings were published today in the latest issue of Nature Communications. The study is the first to illuminate in detail how a particular protein, which is known as CIB2, allows hearing to work.

“We are very excited by these results,” said the senior author of the study, Zubair Ahmed, professor in the Department of Otorhinolaryngology-Head and Neck Surgery at UM SOM. “This tells us something new about the fundamental biology of how hearing works on a molecular level.”

CIB2, which is short for calcium and integrin-binding protein 2, is essential for the structure of stereocilia, the structures at the top of the sensory hair cells in the inner ear. Stereocilia are extremely small, less than a half a micrometer in diameter, which is about the wavelength of a visible light. Each ear contains 18,000 hair cells that do not divide or regenerate.

Dr. Ahmed and his colleague Saima Riazuddin, professor in the Department of Otorhinolaryngology-Head and Neck Surgery at UM SOM, along with their collaborators, discovered five years ago that CIB2 was involved in hearing. Since then, they have studied this protein in flies, mice, zebrafish and humans. The new study is the first to explain the mechanism behind CIB2 in hearing.

In this study, they genetically engineered mice without CIB2, as well as mice in which a human CIB2 gene mutation had been inserted. The researchers found that the human mutation affects the ability of the CIB2 protein to interact with two other proteins, TMC1 and TMC2, which are crucial in the process of converting sound to electrical signals. This process is known as mechanotransduction.

People with this mutation cannot turn soundwaves into signals that the brain can interpret, and so are deaf. When the researchers inserted the human CIB2 mutation into the mouse, they found that the mice were deaf.

“This is a big step in determining the identity of key components of the molecular machinery that converts sound waves into electrical signals in the inner ear,” said the study’s co-senior author, Gregory Frolenkov, of the Department of Physiology at the University of Kentucky.

Dr. Ahmed and his colleagues are now looking for other molecules beyond CIB2 that play a key role in the process. In addition, they are exploring potential therapies for CIB2-related hearing problems. In mice, they are using the gene editing tool CRISPR to modify dysfunctional CIB2 genes. They suspect that if this modification occurs in the first few weeks after birth, these mice, which are born deaf, will be able to hear. The scientists are also experimenting with gene therapy, using a harmless virus to deliver a normal copy of the normal CIB2 gene to baby mice that have the mutated version. Dr. Ahmed says the early results of these experiments are intriguing.

Nearly 40 million Americans suffer from some level of hearing loss. This includes around 74,000 children with profound, early-onset deafness. At least 50 percent of these deafness cases are due to genetic causes.

It is not clear how common CIB2 mutations are in the US population, or how large a role these mutations play in deafness in humans worldwide. In his research on a group of families in Pakistan that have a higher risk of deafness, Dr. Ahmed has found that about 8 to 9 percent seem to have mutations in CIB2. Overall, he says, the gene could play a role in tens of thousands of cases of deafness, and perhaps many more than that. He is also studying CIB2 among the general population. It may be that some versions of the gene also play a role in deafness caused by environmental conditions, creating a predisposition to hearing loss.

Explore further: Deafness genetic mutation discovered

Researchers at the University of Cincinnati (UC) and Cincinnati Children’s Hospital Medical Center have found a new genetic mutation responsible for deafness and hearing loss associated with Usher syndrome type 1.

Mechanosensory hair cells in the inner ear pick up the softest sounds, such as whispers and distant noises.

Ending a 30-year search by scientists, researchers at Boston Children’s Hospital have identified two proteins in the inner ear that are critical for hearing, which, when damaged by genetic mutations, cause a form of delayed, …

A specific protein found in the bridge-like structures that make up part of the auditory machinery of the inner ear is essential for hearing. The absence of this protein or impairment of the gene that codes for this protein …

Scientists at The Scripps Research Institute (TSRI) have discovered how one gene is essential to hearing, uncovering a cause of deafness and suggesting new avenues for therapies.

A new gene therapy approach can reverse hearing loss caused by a genetic defect in a mouse model of congenital deafness, according to a preclinical study published by Cell Press in the July 26 issue of the journal Neuron. …

Although the basic outlines of human hearing have been known for years – sensory cells in the inner ear turn sound waves into the electrical signals that the brain understands as sound – the molecular details have remained …

A new antiviral drug candidate inhibits a broad range of coronaviruses, including the SARS and MERS coronaviruses, a multi-institutional team of investigators reports this week in Science Translational Medicine. The findings …

The billion-year-old primordial system by which early life forms protected themselves against viral infection can still be found in human cells, despite the presence of the much more sophisticated and powerful defense system …

The cell scaffolding holds muscle fibers together and protects them from damage. Individuals who suffer from muscular dystrophy often lack essential components in this cell scaffold. As a result, their muscles lack strength …

Mucus is important for maintaining healthy lungs. Inhaled particles, including bacteria and viruses, get trapped in mucus and then ciliatiny hair like projections on the surface of the airway cellssweep the mucus out …

(Medical Xpress)Via genetic analysis, a large international team of researchers has found rare, damaging gene variants that they believe contribute to the risk of a person developing schizophrenia. In their paper published …

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New research identifies key mechanism behind some deafness – Medical Xpress

Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots – Philadelphia Business Journal

Philadelphia Business Journal
Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots
Philadelphia Business Journal
Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots. Jun 27, 2017, 2:23pm EDT. Industries & Tags: Health Care … Exclusive Online Tools. Research the 3+ year digital archive, and People on the Move leads database download.
Cell, gene therapies are hot. But can this startup make them safer?San Francisco Business Times

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Spark Therapeutics CEO talks drug pricing, gene therapy & his Philadelphia roots – Philadelphia Business Journal