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

Posted: August 9, 2017 at 11:44 pm

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

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

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

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

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

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

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

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

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

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

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Timeline: Gene therapy’s long road to market – Reuters

Posted: August 9, 2017 at 11:44 pm

LONDON (Reuters) - Gene therapy, which aims to patch faulty genes with working DNA, has been a long time in development. The following are major milestones:

1972 - Researchers first suggest gene therapy as a treatment for genetic diseases but oppose its use in humans "for the foreseeable future", pending greater understanding of the technology.

1990 - A four-year-old girl with severe immunodeficiency became the first patient to undergo gene therapy in the United States.

1999 - American patient Jesse Gelsinger dies following a gene therapy experiment, setting the field back several years as U.S. regulators put some experiments on hold.

2002-03 - Cases of leukaemia are diagnosed in French children undergoing gene therapy in a further blow to the field.

2003 - The world's first gene therapy is approved in China for the treatment of head and neck cancer.

2007 - Doctors carry out the world's first operation using gene therapy to treat a serious sight disorder caused by a genetic defect.

2012 - Europe approves Glybera, the first gene therapy in a Western market, for an ultra-rare blood disorder.

2016 - Europe approves Strimvelis for a very rare type of immunodeficiency.

2017 or 2018 - The first gene therapy could be approved in United States.

Reporting by Ben Hirschler; editing by David Stamp

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Bluebird Bio sees Europe as first market for its gene therapies – FierceBiotech

Posted: August 9, 2017 at 11:44 pm

Bluebird Bio plans to bring its gene therapies to market in Europe before the U.S., thanks to a favorable regulatory pathway.

Bluebird's head of Europe, Andrew Obenshain, told the Daily Telegraph that the company is already in negotiations with the EMA and the U.K.'s Medicine and Healthcare products Regulatory Agency (MHRA) on possible regulatory filings.

The EMA's adaptive pathways processwhich allows new therapies to be approved in stages based on stepwise collection of datais a key part of that decision, as is the fact that the agency "works very closely with companies coming forward with new methodologies," said Morgan. And with Brexit looming, it makes sense to discuss these plans with the MHRA separately.

Two years ago, Bluebirdwhich targets severe genetic diseases and cancerwas hit hard when the NorthStar trial of lead therapy LentiGlobin failed to hit the mark in sickle cell disease and beta thalassemia, mainly because of variable patient responses to the treatment.

In a recent SEC filing, the company said that combined data from Northstar and other trials, including a follow-up Northstar-2 study, "could support the filing of a marketing authorization application in the EU" for transfusion-dependent thalassemiaprovided they all meet the primary objective of freeing patients from the need for regular blood transfusions.

So far, no approved gene therapies have been in the U.S., while Europe has seen two approvals, namely for UniGene's Glybera (alipogene tiparvovec) for lipoprotein lipase deficiency and GlaxoSmithKline's Strimvelis for the ultrarare "bubble boy syndrome," or ADA-SCID.

Even getting approval is no guarantee of success, however. Glybera was taken off the market in April due to a lack of demand for the 1 million (around $1.2 million)-per-year therapy, with only one patient receiving it commercially since its launch in 2012.

GSK, meanwhile, has priced Strimvelis at a lower rate (around $650,000 a year) to try to encourage takeup, but hasn't given any updates and said last week it may put its rare disease unit up for sale. Rare disease head Carlo Russo moved to Italian biotech Genenta in January.

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Gene therapy via skin could treat diseases such as obesity – UChicago News

Posted: August 9, 2017 at 11:44 pm

A University of Chicago-based research team has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In a study inthe journal Cell Stem Cell, the researchers provide proof-of-concept. They describe gene-therapy administered through skin transplants to treat two related and extremely common human ailments: Type 2 diabetes and obesity.

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, said study author Xiaoyang Wu, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

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

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

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. We have a better than 80 percent success rate with skin transplantation, Wu said. This is exciting for us.

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

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

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

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid. Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

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

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

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

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

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

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

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

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

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

Additional authors of the study were Japing Yue, Queen Gou, and Cynthia Li from the University of Chicago and Barton Wicksteed from the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society and the V Foundation funded the study.

Article originally appeared on Science Life.

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

Posted: August 9, 2017 at 11:44 pm

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

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

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

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

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

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

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

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

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

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

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

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Testosterone Replacement Therapy – Testosterone Treatment

Posted: August 9, 2017 at 11:43 pm

Testosterone is a major sex hormone produced in the testes of men. The pituitary gland is responsible for controlling the production of testosterone hormone. In the testes, luteinizing hormone binds to receptors on Leydig cells; this stimulates production and secretion of testosterone. Testosterone helps to develop the primary and secondary sexual characteristics in males. Development of sex organs, deeper voice, muscle mass, and facial hair all result from the sufficient production of this hormone. Testosterone deficiency as happens with age needs effective testosterone treatment.

Along with the development of sexual features, testosterone hormone also controls the following actions in a body:

With age, testosterone production declines, thus disturbing overall body functioning. Low levels of testosterone hormone lead to a condition termed as hypogonadism that can be treated with testosterone replacement therapy. Hypogonadism can be divided into two categories depending on the occurrence of pathology.

Primary Hypogonadism: It occurs at testicular level with high release of follicle stimulating hormone (FSH), luteinizing hormone (LH), and low release of testosterone.

Secondary Hypogonadism: It occurs at pituitary hypothalamic level with low or in some cases normal release of luteinizing hormone and follicle stimulating hormone along with low levels of testosterone hormone.

Testosterone replacement therapy effectively works to improve upon the conditions of primary and secondary hypogonadism.

Along with aging, there are some other factors that contribute toward low testosterone production and make a man go for testosterone treatment.

Deficient testosterone hormone levels can lead to many undesirable symptoms, like poor libido, lack of vitality, erectile dysfunction, declining muscle mass, osteoporosis, loss of body hair, depression, lower blood hemoglobin, memory loss, poor concentration, mood swings, mild anemia, disturbed cholesterol profile and a decrease in cognitive function that effects all of your activities. Testosterone therapy is the only possible way to cope with testosterone deficiency.

Before start of the testosterone treatment, there should be the right detection of the hormone deficiency. If you consult an expert doctor for testosterone therapy, he may prescribe you the blood test in the morning because testosterone levels are at peak during that time.

We, at Nationwide Synergy Inc, provide patients with best available options to treat their hormone deficiency.

Choosing one best option for testosterone therapy requires consultation with your physician. We have qualified physicians and doctors at our panel who provide expert guidance to the patients.

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Yes, let’s chat about that first female transgender pro cyclist shall we? – Hot Air

Posted: August 9, 2017 at 11:43 pm

Weve had a seemingly endless series of discussions about the various aspects of the transgender debate here, many of which focus on the continued and worrisome spread of normalization gender dysphoria in society, the military and beyond. But one of the side-bar aspects of this discussion has had to do with the world of sports. Whether youre talking about a girl wrestling against boys or comparing the Bobby Riggs vs Billy Jean King tennis match to Renee Richards, questions of gender bending in the competitive arena come with all sorts of complications.

Now another sport is being featured in this ongoing debate and its the world of competitive cycling. For the first time a man identifying as a woman will be racing in a USA Cycling sanctioned event in the womens category and competing against some of the top female cyclists. Jillian Bearden (formerly Jonathan) is going to be competing in the Colorado Classic and is able to do so because both the International Olympic Committee and Cycling USA have removed the requirement for transgender athletes to have their transition surgery prior to being able to compete. What theyve done instead is require that men transitioning to be women spend at least one year on medication to suppress their testosterone production, increase estrogen and keep their T levels below a certain, unspecified level. (It will come as no surprise that there are no parallel testing requirements for women identifying as men.) From theDenver Post:

The new rules simply require transwomen to keep testosterone below a certain level for a year before competing and must present a doctors note showing their testosterone levels are below the IOC threshold. The IOC recommendations include no restrictions for athletes transitioning to male.

USA Cycling was one of the first national governing bodies to embrace the new policy, thanks in part to Beardens help. She had the science to support the new rules.

As an elite male racer, she had regular benchmarks measuring her power and lactate threshold. After more than two years of blocking testosterone and boosting estrogen, her wattage output has dropped by 11.4 percent. That mirrors the performance gap between top-tier male and female athletes.

Bearden has done precisely that and claims that his performance has decreased substantially from his days cycling as a man. Because of that, the argument goes, theres no problem with him having any sort of unfair advantage.

Bearden has watched her performance ebb since beginning hormone-replacement therapy in 2015. As testosterone fades and estrogen grows, her fastest times on favorite climbs have slipped into what she calls the gutter.

It was tough realizing her hard-earned power, developed over more than a decade of elite-level bike racing, was waning.

I went from 16 minutes to 26, 27, 28 minutes, she said of her times on her those climbs. I was like holy Testosterone gives you this drive, this oomph, and I didnt have that push.

Ill confess I hadnt given much thought to this aspect of it. The difference in performance levels between men and woman in all of these sports is well known, and letting a guy compete with the women would be grossly unfair. But if you suppress his testosterone levels enough, will his performance really degrade far enough to keep things competitive?

Hed better have suppressed it a lot. I was looking over some of the current records for cycling in the 24 hour competitions on both road and track. (Thats the distance you can ride in 24 hours.) The womens road record currently stands at just under 470 miles. The mens record? 557 miles. The indoor and outdoor track records similarly have a disparity of one hundred miles or more in the mens favor. Is a vastly decreased T level enough to make that much of a difference? While its not being applied to gender dysphoria situations, several medical resources indicate that markedly lower levels have an impact, but precisely how much is unknown and can vary from individual to individual.

Because testosterone plays a role in building muscle, men with low T might notice a decrease in muscle mass. Studies have shown testosterone affects muscle mass, but not necessarily strength or function.

The major problem here is that we dont have a baseline to study. Because of a lack of professional or Olympic records (at least as far as I can find and they arent mentioned in the Denver Post article) we have no idea how great of a cyclist Jonathan Bearden was before he started riding as Jillian Bearden. If he winds up coming in at the back or in the middle of the pack Im sure everyone will be all smiles and say it was great having him in the race. But what has that really proved? The best woman cyclist in the world will no doubt be able to smoke a mediocre male rider while the top flight men would leave her in the dust based on current Olympic records. Were looking at a situation similar in some ways to the aforementioned tennis scenario with Renee Richards. Keep in mind that he was in his mid to late 30s already by the time he was entering tennis full time and was certainly competent, but was only ranked in the top 20 in the over 35 category. Yet when playing as a woman Richards reached a ranking of 20th overall (against the best female players of any age) in 1979 and reached the womens doubles finals at the US Open that year.

That leaves us with an open question as to how well hell do in this race and, perhaps more importantly, how well hell be received. Its been a rousing and supportive welcome thus far, but if Bearden waltzes in there and wins (or comes fairly close) having no real racing bona fides beforehand, do you suppose all of the female competitors are still going to be quite so supportive and welcoming?

Stay tuned. Well have some of those answers later this month.

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Trans athlete proves transition is more than a name change – Colorado Daily

Posted: August 9, 2017 at 11:43 pm

SALIDA Less than three years into her transition from Jonathan to Jillian, pro cyclist Jillian Bearden has once again found serenity on her bike. Now, using studies and stats collected during her long career, she's helping prove that transgender athletes change more than their names; they change their biology.

Bearden has watched her performance ebb since beginning hormone-replacement therapy in 2015. As testosterone fades and estrogen grows, her fastest times on favorite climbs have slipped into what she calls "the gutter."

It was tough realizing her hard-earned power, developed over more than a decade of elite-level bike racing, was waning.

Jillian Bearden will race in the Colorado Classic, her highest-level event ever after winning the Tour of Tuscon in her big-race debut as a female racer last fall. (Hyoung Chang / The Denver Post)

"I went from 16 minutes to 26, 27, 28 minutes," she said of her times on her those climbs. "I was like holy ... Testosterone gives you this drive, this oomph, and I didn't have that push. My muscles looked fairly big, but I did not have that push to drive that extra energy. I had good days and really, really bad days. But at the end of it all, I always know that I won the biggest race of all. I am here on planet Earth with my family, and it doesn't really matter how slow I am. I've already won."

On Thursday, when Bearden saddles up with the world's best female cyclists for the Colorado Classic in her hometown of Colorado Springs, she will be the first transwoman to race with a pro peloton in the United States. Thanks to recently relaxed International Olympic Committee rules governing transgender athletes, and USA Cycling's embrace of those new rules, Bearden has become a beacon for transathletes across the globe.

Bearden is basking in a light that saved her life. In late 2014, she was driving in the dark and pushed her car to 90 mph. She turned up her favorite tune and prepared to whip the steering wheel and end it all. The darkness was all-consuming, eclipsing all the outward trimmings of success: a family, a home, a job and elite-level talent on a bike.

But just before that fateful yank, Bearden said she felt "an angelic light" penetrate her overwhelming misery. Maybe it was from her mom. Or her brother, who had taken his life almost a decade earlier.

"Whatever it was, that presence brought me out, and the message to me was, 'Tell your mom. Just tell your mom,'" Jillian said.

Jillian told her mom. Then she told her spouse. And her kids. And now she's telling the world that, since her birth, despite the misplaced hardware and the name Jonathan, she is a woman. It's not just that she always wanted to be a woman. She is a woman.

"I would have killed myself that night, and no one would have ever known why. I always knew who I was, but I was in such turmoil," the 36-year-old said, sipping coffee before a high-speed criterium race on rain-soaked streets in Salida.

While she was ready to sacrifice her competitive life in the saddle to claim her gender, she wasn't going to let go of bike racing without a fight. Cycling is her therapy, she said.

"Riding my bike has saved my life many times over," said Bearden, who works as an electrical engineer.

After her brother killed himself in 2005, she pedaled. As she grappled with her gender dysphoria, she pedaled. When suicidal thoughts consumed her, she pedaled. After several thousand hours of training and racing, she was really good. By the time she came so close to ending her life, she had reached the highest levels of amateur cycling on both her mountain and road bikes. Racing was part of her identity. Staying competitive on the bike was vital as she transitioned.

Her growth to Jillian has included more than counseling: hormone therapy to block testosterone and add estrogen, laser hair removal and a public pivot to female. She's also worked with the IOC and USA Cycling to implement new rules for transgender athletes.

The IOC's 2003 rules governing transgender athletes required them to have gender-reassignment surgery to compete in Olympic sports.

"To require surgical anatomical changes as a precondition to participation is not necessary to preserve fair competition and may be inconsistent with developing legislation and notions of human rights," reads the IOC's November 2015 draft guidelines for transgender policies.

The new rules simply require transwomen to keep testosterone below a certain level for a year before competing and must present a doctor's note showing their testosterone levels are below the IOC threshold. The IOC recommendations include no restrictions for athletes transitioning to male.

USA Cycling was one of the first national governing bodies to embrace the new policy, thanks in part to Bearden's help. She had the science to support the new rules.

As an elite male racer, she had regular benchmarks measuring her power and lactate threshold. After more than two years of blocking testosterone and boosting estrogen, her wattage output has dropped by 11.4 percent. That mirrors the performance gap between top-tier male and female athletes.

Bearden says those results have fostered a welcoming environment among her fellow racers. And with her decrease in power documented, she's able to dismiss the argument that she's carrying her years of training and racing as a man into women's racing.

"I'm shocked and I'm blessed and so happy they have embraced me and bought me in and treated me like who I am: a woman," she said. "I think a lot of people have read about my work with the IOC and USAC, and they see my test results from before and after and they see me as legit. I mean, I'm here. I'm a woman. Let's race."

Michelle Henry, a Palmares Racing teammate, has been training with Bearden for several weeks to prepare for the Colorado Classic.

"There are a lot of us who really support her," she said. "As much as her mission is to help others who might be struggling through that really low spot she was in, for many of us, we want to help those people understand there is a lot of acceptance out there and we support them."

Bearden credits the support of her team and family with her mental fight to regain her competitive edge. As her power waned, her push became much more internal.

"The testosterone is gone, so you have to find a new way to get to the new you, and the new me was working on my mental game," she said. "Now it's all mental."

Bearden's steep decline in performance aligns with the first study of transgender athletes, published in 2015 in the Journal of Sporting Cultures and Identities by medical physicist Joanna Harper, who is advising the IOC on its transgender policies. Harper's study showed transwomen runners slowed and lost strength as they blocked testosterone and added estrogen.

Chuck Hodge, the technical director for USA Cycling, consulted with Bearden as American cycling's governing body crafted a policy that welcomed all athletes. With the IOC revising its recommendations for transwomen athletes, USA Cycling didn't need to go through a philosophical or political review, he said, so much as embrace "an update that really modernized our view.

"We basically said this is our policy and this is what's fair and this is what we are doing," he said.

Hodge worked with Bearden through tweaks, like making sure her former name didn't pop up with her times on a race's online results page. "That sounds small, but I can't imagine going through all these changes and then our automated system throws up their old name. Jillian has been very helpful and understanding through the process."

Hodge said he's been "somewhat shocked at the number of calls and emails" from athletes who are following Bearden's lead.

"This wasn't a hard decision," he said. "It's really just treating people fairly and equitably and with respect."

USA Cycling is at the forefront of Olympic-sport governing bodies that are crafting policies for transgender athletes. Athletes like Bearden, with her before-and-after power data, support more science-based decisions, said Ashland Johnson, the director of education and research at the Human Rights Campaign who recently conducted a training for U.S. Olympic Committee coaches and administrators to help embrace athletes of every stripe.

"We are seeing more of a move among governing bodies, where instead of making policies that are dependent on old stereotypes based on gender, decisions are based in science, inclusion and fairness," she said.

Things are moving in the right direction at the international and national level, but more needs to be done at the state level to make sure the Olympic pipeline of younger athletes can include transgender competitors, Johnson said.

"That K-12 arena is where everyone should be able to participate," Johnson said. "We want to increase inclusion at every level of sport, but especially K through 12."

Even with the welcome from her fellow competitors and her rising profile as a transathlete role model, Bearden is quick to admit that not one step of her journey has been easy. But it's better than it ever was.

Last fall, with her wife, Sarah, and their almost 3-year-old daughter cheering her on, she won Arizona's El Tour de Tucson, one of the largest road bike races in the country. The Trans National Women's Cycling Team she co-founded last year has 22 members from 15 states and Mexico. So far this season, she's competed in almost 20 races in Colorado and the West. In late July, she placed fifth in the Salida Classic criterium. The next day, she took third in the event's road race.

The Colorado Classic will be her highest-profile competition.

She's a podium contender, and she's ready for the hate that might bring. She got it aplenty after she won the Tucson race. Her Facebook and Strava pages were quickly stained with anonymous commenters seemingly irked by her talent. Recently, she's had to report online death threats to the police. Transwomen are disproportionately targeted for violence, and transgender people have a high suicide rate, with an estimated 41 percent of transgender adults saying they have attempted to kill themselves.

But for every bucketload of hostility, Bearden says she connects with one person who is inspired by her story. That makes it all worth it, she said. Since she began racing last year, she's developed friendships with more than 50 transgender cyclists across the world eager to follow her lead.

As more step forward to claim their gender, she said, momentum is building.

"I want to use the strength I was given through my transition and send ripples to people everywhere. At the end of the day, it could help save a life for someone in a dark place," she said. "I'm hoping that me being out in the public eye can give people the courage and safety to come out and do what they love and be who they are."

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Asterias Enrolls First Patient in Final Cohort of SCiStar Clinical Trial – GlobeNewswire (press release)

Posted: August 9, 2017 at 11:42 pm

FREMONT, Calif., Aug. 09, 2017 (GLOBE NEWSWIRE) -- Asterias Biotherapeutics, Inc. (NYSE MKT:AST), a biotechnology company pioneering the field of regenerative medicine, today announced enrollment and dosing of the first patient in the fifth and final cohort in the companys ongoing SCiStar Phase 1/2a clinical study of AST-OPC1 in motor complete cervical spinal cord injury (SCI). This cohort will dose between five and eight patients with AIS-B (motor complete, sensory incomplete) cervical spinal cord injuries with 20 million AST-OPC1 cells.

Enrollment in our SCiStar study has accelerated over the last several quarters as evidenced by the completion of enrollment of the third and fourth cohorts in July, and now the dosing of the first patient in the fifth and final cohort immediately after clearing the 30-day waiting period required by our study protocol, said Dr. Edward Wirth, Chief Medical Officer of Asterias. We remain on pace to complete enrollment of the entire SCiStar study by the end of 2017.

Asterias has completed enrollment and dosing in four of the five planned SCiStar study cohorts and has enrolled twenty-two patients in the SCiStar study. Twenty-seven patients have been administered AST-OPC1 after including patients from a previous Phase 1 safety trial and results-to-date continue to support the safety of AST-OPC1. In June 2017, Asterias reported 9-month data from the studys second dose cohort (AIS-A patients dosed 10 million cells). Subjects in this cohort showed meaningful improvements in arm, hand and finger function that were first observed at 3-months after administration of AST-OPC1, and were maintained and further increased at up to 9-months. The company expects multiple safety and efficacy readouts from the SCiStar study during the remainder of 2017 and 2018.

About the SCiStar Trial

The SCiStar trial is an open-label, single-arm trial testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with subacute, C-4 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may have retained some minimal sensory function below their injury site. AST-OPC1 is being administered 21 to 42 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product.

The study is being conducted at eight centers in the U.S. and the company plans to increase this to up to 12 sites to accommodate the expanded patient enrollment. Clinical sites involved in the study include the Medical College of Wisconsin in Milwaukee, Shepherd Medical Center in Atlanta, University of Southern California (USC) jointly with Rancho Los Amigos National Rehabilitation Center in Los Angeles, Indiana University, Rush University Medical Center in Chicago, Santa Clara Valley Medical Center in San Jose jointly with Stanford University, Thomas Jefferson University Hospital in partnership with Magee Rehabilitation Hospital in Philadelphia, and UC San Diego Health in San Diego, California.

Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Additional information on the Phase 1/2a trial, including trial sites, can be found at http://www.clinicaltrials.gov, using Identifier NCT02302157, and at the SCiStar Study Website (www.SCiStar-study.com).

About AST-OPC1

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells originally isolated in 1998, has been shown in animals and in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. Based on the results of this study, Asterias received clearance from FDA to progress testing of AST-OPC1 to patients with cervical spine injuries in the current SCiStar study, which represents the first targeted population for registration trials. Asterias has completed enrollment in the first four cohorts of this study. Results to date have continued to support the safety of AST-OPC1. Additionally, Asterias has recently reported results suggesting reduced cavitation and improved motor function in patients administered AST-OPC1 in the SCiStar trial.

About Asterias Biotherapeutics

Asterias Biotherapeutics, Inc. is a biotechnology company pioneering the field of regenerative medicine. The company's proprietary cell therapy programs are based on its pluripotent stem cell and immunotherapy platform technologies. Asterias is presently focused on advancing three clinical-stage programs which have the potential to address areas of very high unmet medical need in the fields of neurology and oncology. AST-OPC1 (oligodendrocyte progenitor cells) is currently in a Phase 1/2a dose escalation clinical trial in spinal cord injury. AST-VAC1 (antigen-presenting autologous dendritic cells) is undergoing continuing development by Asterias based on promising efficacy and safety data from a Phase 2 study in Acute Myeloid Leukemia (AML), with current efforts focused on streamlining and modernizing the manufacturing process. AST-VAC2 (antigen-presenting allogeneic dendritic cells) represents a second generation, allogeneic cancer immunotherapy. The company's research partner, Cancer Research UK, plans to begin a Phase 1/2a clinical trial of AST-VAC2 in non-small cell lung cancer in 2017. Additional information about Asterias can be found at http://www.asteriasbiotherapeutics.com.

FORWARD-LOOKING STATEMENTS

Statements pertaining to future financial and/or operating and/or clinical research results, future growth in research, technology, clinical development, and potential opportunities for Asterias, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, uncertainty in the results of clinical trials or regulatory approvals, need and ability to obtain future capital, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the businesses of Asterias, particularly those mentioned in the cautionary statements found in Asterias' filings with the Securities and Exchange Commission. Asterias disclaims any intent or obligation to update these forward-looking statements.

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Asterias Enrolls First Patient in Final Cohort of SCiStar Clinical Trial - GlobeNewswire (press release)

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NSF EPSCoR awards new projects – Gears Of Biz

Posted: August 9, 2017 at 11:41 pm

The National Science Foundation (NSF) has made eight awards totaling $41.7 million for projects aimed at building capacity to research a national priority area: understanding the relationship in organisms between genetic material, or genotype, and physical characteristics due to gene expression and environmental influences, or phenotype.

The genotype-to-phenotype relationship has significant societal and economic implications across scientific fields and areas of industry, including but not limited to medicine, agriculture, biotechnology and ecology. An enhanced understanding of this relationship holds the potential for improved food crop yields, better prediction of human disease risk and new drug therapies. Through these investments, NSF aims to provide the scientific community with new tools and resources for future discoveries.

Over the past several decades, scientists and engineers have made massive strides in decoding, amassing and storing genomic data, said Denise Barnes, Head of NSFs Established Program to Stimulate Competitive Research (EPSCoR) Program. But understanding how genomics influence phenotype remains one of the more profound challenges in science. These awards lay the groundwork for closing some of the biggest gaps in biological knowledge and developing interdisciplinary teams needed to address the challenges.

The awards are made through NSF EPSCoR as part of its Research Infrastructure Improvement (RII) Track-2 investment strategy. RII Track-2 is intended to build national research strength by initiating research collaborations across institutions in two or more EPSCoR jurisdictions. The four-year awards involve 21 institutions in 16 eligible jurisdictions.

EPSCoR is a program designed to fulfill NSFs mandate to promote scientific progress nationwide. Currently, 24 states, the Commonwealth of Puerto Rico, the U.S. Virgin Islands and Guam are eligible to compete for EPSCoR RII funding. Through this program, NSF establishes regional partnerships with government, higher education and industry that create lasting improvements in a states or territorys research infrastructure and research and development capacity.

Each of the new awards will support research and require recipient institutions to invest in developing a highly skilled, diverse workforce particularly early-career faculty researchers that can sustain research development in science, technology, engineering and mathematics (STEM) both in academia and in industry.

This years eight awards are for four years each and involve 21 institutions in 16 EPSCoR-eligible jurisdictions.

The project titles, principal investigators and lead institutions are listed below.

Using Natural Variation to Educate, Innovate, and Lead (UNVEIL): A collaborative research network to advance genome-to-phenome connections in the wild: Zac Cheviron, University of Montana

This project capitalizes on complementary research strengths at the University of Montana and the University of Nebraska-Lincoln to address fundamental scientific questions that can advance understanding of how organisms function in complex environments and how they acclimate and adapt to environmental challenges. The team seeks to use newly developed genomic technologies to understand the genetic basis of traits that influence the survival of wild animals and plants in changing environments. Their findings will have major implications that extend to conservation biology, agriculture and medicine.

Comparative genomics and phenomics approach to discover genes underlying heat stress resilience in cereals: Harkamal Walia, University of Nebraska-Lincoln

To ensure global food security, there is an urgent need to improve crop resilience to high night-temperature stress-induced losses to yield and quality. This project will focus on rice and wheat, which together provide more than 50 percent of caloric intake for humans worldwide. This project builds upon complementary expertise and infrastructure in Nebraska, Kansas and Arkansas for studying rice and wheat crops at the laboratory and field scales. The project will translate these discoveries into genetic and phenotypic markers for public and private breeding programs and develop a broad continuum for plant science research and education. Collaboration with key industry partners will ensure the prompt translation of promising research findings into applications that can benefit farmers.

Genome to fitness: An analysis of the stress response in Peromyscus: Hippokratis Kiaris, University of South Carolina at Columbia

This collaborative project involving the University of South Carolina, Claflin University and Auburn University aims to dissect the genomic basis of stress response in mammals. The stress responses vary among cells and tissue types and the impact of these responses on animals functions and survival is not well understood. This project applies a combination of genomic analyses coupled with stress tests at cellular and organismal levels to understand the fitness of mammals. The research will use the North American deer mouse as a model.

Advanced biomanufacturing: Catalyzing improved host development and high-quality medicines through genome to phenome predictions: Sarah Harcum, Clemson University

This project brings together Clemson University, the University of Delaware, Tulane University and Delaware State University to study the basis for genomic instability in ovary cell lines, using the Chinese hamster as the organism for study. The study aims to expand the quantitative understanding of the complex interactions between the genome and environment that generates variable phenotypes. A lack of understanding of the fundamental link between genome stability and the phenome significantly limits the ability to improve cell lines. This study will provide foundational genotype-phenotype knowledge to overcome those limitations, thus solving biopharmaceutical manufacturing challenges to improve medicines and patient access to medicines.

Using biophysical protein models to map genetic variation to phenotypes: Frederick Ytreberg, University of Idaho

One of the great challenges in modern biology is understanding how changes in amino acids that are the building blocks of proteins lead to changes in the characteristics of a living organism. This project tackles this aspect of the genotype-phenotype challenge by focusing on protein biophysical models and using a diverse set of experimental systems, molecular and mathematical modeling. The project builds upon complementary expertise and infrastructure in Idaho, Vermont and Rhode Island. The research has significant societal implications for its potential to lead to advances in biotechnology and health sciences.

Building Genome-to-Phenome Infrastructure for Regulating Methane in Deep and Extreme Environments (BuG ReMeDEE): Rajesh Sani, South Dakota School of Mines and Technology

Globally, about 60 percent of methane emissions are related to human-caused activity. Most of those human-related emissions are attributed to microbes involved with the decomposition of biomass, including waste in landfills and sediment at the bottom of bodies of water. However, a large gap in scientific knowledge is associated with methane cycles in deep, extreme areas of Earths biosphere. The BuG ReMeDEE consortium brings together experts from South Dakota School of Mines and Technology, Montana State University and University of Oklahoma to investigate methane cycling in such environments and develop new biological mechanisms for converting methane into value-added products.

Genomic logic underlying adaptive morphological divergence: Riccardo Papa, University of Puerto Rico Rio Piedras

Understanding the genotype-phenotype relationship is an important goal for evolutionary biology, but it remains a challenge due to the complexity of interpreting the connections between networks of interacting genes and evolutionary development mechanisms. This project builds on the complementary expertise of the University of Puerto Rico-Rio Piedras and Mississippi State University and uses butterfly wing color patterns as a mechanism to study genotype-phenotype relationships in Heliconius butterflies. Disentangling these relationships will provide a major advance in understanding how morphological diversity develops and ultimately originates, which would inform research into other organisms.

G2P in VOM: An experimental and analytical framework for genome to phenome connections in viruses of microbes: Eric Wommack, University of Delaware

The proposed research will test genome to phenome hypotheses in viruses of microbes, focusing on phenomic features influencing viral impacts within ecosystems. Viruses are now known to play important and possibly indispensable roles in the biology and ecology of cellular organisms. Most viruses observed within ecosystems infect microbes. During infection, viruses can alter the phenome of host cells in ways that change the population biology of microbial communities and the flow of nutrients and energy within ecosystems. The details of these processes are largely a mystery. This project will work to connect the genomic features of viruses of microbes with phenotypic life-history traits, using these connections to advance scientific understanding about the role of such viruses in ecosystems. The team is formed by experts from University of Delaware, the University of Nebraska-Lincoln, the University of Hawaii at Manoa and a primarily undergraduate university in Rhode Island, Roger Williams University.

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