There are genetic differences when comparing prostate tumors from African American men and European-American men, but none of these differences are of clinical significance for the genetically targeted treatments available to date, according to an analysis published in Clinical Cancer Research.

"[N]o significant differences were seen in clinically actionable DNA repair genes, MSI-high [microsatellite instabilityhigh] status, and tumor mutation burden, suggesting that current therapeutic strategies may be equally beneficial in both populations," wrote study author Yusuke Koga, of the Boston University, and colleagues.

"Since these findings suggest that the frequency of targetable genetic alterations is similar in patients of predominantly African versus European ancestry, offering comprehensive genomic profiling and biomarker-based therapies to all patients, including African American patients, is a critical component of promoting equity in the management of metastatic prostate cancer," said Atish D. Choudhury, MD, PhD, of the Dana-Farber Cancer Institute in Boston, who was not involved in this study.

Mr. Koga and colleagues noted that, when compared with European-American men, African American men have a higher incidence of prostate cancer, present with more advanced disease at an earlier age, and have increased mortality. These differences persist even after adjustment for socioeconomic covariates. That raises the question of the role of genetics.

"There is emerging evidence that, across some clinical trials and equal-access health systems, outcomes between AFR [African-American] men and European-American men with prostate cancer are similar," the investigators wrote. "Although these data suggest that disparities can be ameliorated, there is limited knowledge of the genomic alterations that differ between groups and that could impact clinical outcomes."

To get a handle on the issue, the investigators performed a meta-analysis of tumors from 250 African American men and 611 European-American men to compare the frequencies of somatic alterations across datasets from the Cancer Genome Atlas, the African Ancestry prostate cancer cohort, and the Memorial Sloan KetteringIntegrated Mutation Profiling of Actionable Cancer Targets panel.

The team also compared prostate cancer sequencing data from a commercial platform, the Foundation Medicine assay, from 436 African-American men and 3,018 European-American men.

In the meta-analysis, mutations in ZFHX3 and focal deletions in ETV3 were more common in tumors from African American men than in tumors from European-American men. Both genes are putative prostate cancer tumor suppressors, the investigators noted.

TP53 mutations, meanwhile, were associated with increasing Gleason scores in both groups, suggesting "that if TP53 mutations are found in low-grade disease, they may potentially indicate a more aggressive clinical trajectory," the investigators wrote.

In the analysis with the commercial assay, MYC amplifications were more frequent in African American men with metastatic disease, raising "the possibility that MYC amplifications may also contribute to high-risk disease in this population," the team wrote.

Deletions in PTEN and rearrangements in TMPRSS2-ERG were less frequent in tumors from African American men, but KMT2D truncations and CCND1 amplifications were more frequent.

"Higher expression of CCND1 has been implicated with perineural invasion in prostate cancer, an aggressive histological feature in prostate cancer. Truncating mutations in KMT2D have been reported in both localized and metastatic prostate cancer patients with unclear clinical significance," the investigators noted.

"The genomic differences seen in genes such as MYC, ZFHX3, PTEN, and TMPRSS2-ERG suggest that different pathways of carcinogenesis may be active in AFR [African American] men, which could lead to further disparities if targeted therapies for some of these alterations become available," the team wrote.

They noted that the meta-analysis was limited by the fact that some cohorts lacked matched tumors from European-American men, which limited the investigators' ability to control for differences in region, clinical setting, or sequencing assay. Furthermore, age, tumor stage, and Gleason grade were unavailable in the cohort analyzed with the commercial assay.

This research was funded by the Department of Defense, the National Cancer Institute, and the Prostate Cancer Foundation. Two authors are employees of Foundation Medicine.

SOURCE: Koga Y et al. Clin Cancer Res. 2020 Jul 10. doi: 10.1158/1078-0432.CCR-19-4112.

This article originally appeared on MDedge.com.

See more here:

Genetic Differences by Ancestry and Prostate Cancer Therapies - Medscape

Message from the Director

As NIDDK celebrates its 70th anniversary, we look back on decades of scientific advances and forward to what we will achieve in the decades to come. Discovery and innovation are at the core of our institute, the result of the dedication and talent of our staff and grantees. Our achievements together have led to better ways to prevent and treat conditions among the countrys greatest public health concerns, including diabetes, obesity, kidney diseases, and many others in our diverse mission. I invite you to read about some of these advances in the links below and to follow the development of our strategic plan, which will guide how NIDDK will maximize public investment in research and amplify efforts where needed the most.

This year weve faced remarkable challenges, as a global pandemic upended life as we know it. NIDDK staff, grantees, and trainees have risen to that charge at every step, joining the search for ways to combat COVID-19 or pioneering solutions to keep operations running smoothlydespite many uncertainties. With a strengthened spirit of community, we embark on the next 70 years with compassion and determination to preserve and advance public health.

- Griffin P. Rodgers, M.D., M.A.C.P.

Click anywhere on the NIDDK social media messages below to then like and share the posts on your Facebook and Twitter pages

Download our NIDDK 70th Anniversary Social Media Graphics (ZIP, 749.08 KB) and content to post on your Instagram , Facebook, and Twitter pages.

Over the past 70 years, NIDDK has made substantial scientific research advancements and our scientists have been honored with prestigious awards for their work to improve public health. Looking forward, we strive to discover better ways to help manage and treat diseases central to our missions. Learn more about NIDDK and its advances in the NIH almanac.

October 16, 1968 Dr. Nirenberg of the National Heart Institute shared the Nobel Prize in Physiology or Medicine with two other scientists. Dr. Nirenberg reported his celebrated partial cracking of the genetic code while an NIAMD scientist.

October 1972 Dr. Afinsen, chief of the Institutes Laboratory ofChemical Biology, shared the Nobel Prize in Chemistry with twoother American scientists for demonstrating one of the mostimportant simplifying concepts of molecular biology: that the threedimensionalconformation of a native protein is determined by thechemistry of its amino acid sequence. A significant part of theresearch cited by the award was performed while Anfinsen was withthe NIH.

November 1982 Dr. Neufeld, chief of the NIADDKs genetics andbiochemistry branch, received the Albert Lasker Clinical MedicalResearch Award. She was cited, along with Dr. Roscoe O. Brady ofthe then-named National Institute of Neurological andCommunicative Disorders and Stroke, for their contributions to theunderstanding and diagnosis of inherited diseases calledmucopolysaccharide storage disorders.

September 2010 Dr. Friedman, a NIDDK grantee and formergrantee Dr. Douglas Coleman won the Albert Lasker Basic MedicalResearch Award for discovering the hormone leptin, which plays akey role in regulating energy intake and energy expenditure.

September 21, 2012 Dr. Starzl, a longtime NIDDK grantee, receivedthe Lasker-DeBakey Clinical Medical Research Award, shared withanother scientist for his work developing liver transplantation, anintervention that has restored normal life to thousands of peoplewith end-stage liver disease.

September 2016 Dr. Semenza, a NIDDK grantee, shared the AlbertLasker Basic Medical Research Award with NIH grantee Dr. WilliamG. Kaelin Jr. and another scientist for their discovery of the pathwayby which cells from humans and most animals sense and adapt tochanges in oxygen availabilitya process essential for survival.

October 7, 2019 NIDDK grantee Dr. Semenza shared the Nobel Prizein Physiology or Medicine with NIH grantee Dr. William G. Kaelin Jr.and another scientist for their discoveries of how cells sense andadapt to oxygen availability.

Chronic liver disease can result from many causes, the two most common being viral hepatitisincluding hepatitis B, C, and Dand nonalcoholic fatty liver disease (NAFLD). NIDDK-supported research has yielded important knowledge that has improved the lives of people with many forms of chronic liver disease.

Over the past several decades, NIDDK has supported research to improve our understanding of Inflammatory Bowel Disease (IBD) through development of new approaches to study IBD and genetics, gut microbiome research, and personalized treatments for patients with IBD.

An estimated 37 million American adults have Chronic Kidney Disease (CKD), and kidney diseases are the ninth leading cause of death in the United States. NIDDKs continued development and testing of new detection strategies, therapies, and community education helps support the health and quality of life of people with CKD.

Nutrition plays a fundamental role in sustaining health and preventing disease. The NIDDK supports an extensive and collaborative portfolio in nutrition research, including clinical studies of diet and nutrition, microbiomes, and precision approaches to dietary recommendations.

Obesity has risen to epidemic levels in the United States and it is a major public health challenge. NIDDK-supported research has improved our understanding of body weight regulation and yielded new treatment approaches for people with obesity.

NIDDK-funded research has made important strides in developing new treatments for diseases like Sickle Cell Disease and understanding anemia. Recently, research into how cells detect oxygen and react to low oxygen levels was selected as the 2019 Nobel Prize in Physiology or Medicine.

NIDDK-supported research has led to critical knowledge in areas of intensive glucose control, preventing type 1 diabetes and improving longevity of people with the disease.

NIDDK research seeks to reduce the burden of this serious and all too common disease with findings shown to prevent, delay, and treat T2D in high-risk people or those living with the disease. NIDDK research also focuses its efforts in gestational diabetes studies and T2D in special populations.

The Healthy Moments celebration of NIDDKs 70th anniversary features five talks with NIHDirector, Dr. Francis Collins.

Episode 1: Creating Medical Devices to Improve Treatment of Type 1 Diabetes

Episode 2: Using Genetics to Improve Treatment of Type 2 Diabetes

Episode 3: Fighting Kidney Disease with Precision Medicine

Episode 4: Decoding the Burden of Inflammatory Bowel Disease

Episode 5: Making Obesity Treatment More Personal

Healthy Moments is a weekly broadcast that provides listeners reliable, science-based,healthy lifestyle tips, actionable suggestions, and other important health informationfeaturing Dr. Griffin Rodgers, Director of NIDDK. View more Healthy Moments episodes.

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NIDDK 70th Anniversary (1950-2020) | NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

CAMBRIDGE, Mass., July 24, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that theU.S. Food and Drug Administration(FDA) has granted Fast Track designation to SRP-9001 (AAVrh74.MHCK7.micro-dystrophin). SRP-9001 is an investigational gene transfer therapy intended to deliver its micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Safety and tolerability data at one year from four clinical trial participants who received SRP-9001 in Study 101 were recently published in JAMA Neurology, and Study 102, a randomized, double-blind, placebo-controlled study of SRP-9001, is ongoing with results expected in early 2021.

The Fast Track designation is a process designed to facilitate the development and expedited review of drugs that treat serious conditions and fill unmet medical needs.In addition to Fast Track, SRP-9001 has also been granted Rare Pediatric Disease (RPD) designation. SRP-9001 was previously granted Orphan Drug status in the United States, the European Union and Japan.

About SRP-9001

SRP-9001 is an investigational gene transfer therapy designed to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States. In December 2019, the Company announced a licensing agreement granting Roche the exclusive right to launch and commercialize SRP-9001 outside the United States. Sarepta has exclusive rights to the micro-dystrophin gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Childrens Hospital.

AboutSarepta TherapeuticsAt Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visitwww.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.

Forward-Looking StatementsThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding SRP-9001s intention to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein; Sareptas expectation to have results from Study 102 in early 2021; and Sareptas plan to commercialize SRP-9001 in the United States.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sareptas control. Known risk factors include, among others: fast track designation by the FDA may not lead to faster development or regulatory review or approval process, and does not increase the likelihood that SRP-9001 will receive marketing approval; Sarepta may not be able to complete clinical trials required by the FDA or other regulatory authorities for approval of SRP-9001; SRP-9001 may not result in a viable treatment suitable for commercialization due to a variety of reasons including the results of future research may not be consistent with past positive results or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; Sarepta may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans, and bringing its product candidates to market, due to a variety of reasons, many of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates and the COVID-19 pandemic; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2019, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by Sarepta which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect Sareptas business, results of operations and the trading price of Sareptas common stock. For a detailed description of risks and uncertainties Sarepta faces, you are encouraged to review the SEC filings made by Sarepta. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website atwww.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

Original post:

Sarepta Therapeutics Receives Fast Track Designation for SRP-9001 Micro-Dystrophin Gene Therapy for the Treatment of Duchenne Muscular Dystrophy -...

From time to time, Ann would notice qualities in Deniseher smarts, her athleticism, her bright blue eyesand think, she must have gotten that from her donor. She secretly hoped that one day Denise would track him down. She knew it was a long shot, though. The clinic hadnt even given her the donor number.

Norman succumbed to his drinking, and in 2010, at age 60, he died from cirrhosis of the liver. Denise was 32. Freed from her promise of secrecy, Ann prepared to tell her daughter the truth. Arriving home with the family after her youngest daughters graduation, Ann announced she had news. A thought came to Denise, as if from someone elses mind. Shes going to tell me my dad isnt my real dad. It took her aback. The idea had never occurred to her before.

Ann told her about the mumps, the infertility, the Birmingham clinic, the donor. She handed Denise the receipt from the clinicfor a couple hundred dollarsand a clipping from the Donor Sibling Registry, an organization that launched in 2000 to connect offspring to their donors and siblings. She hoped that Denise could use it to track down her biological father.

But Denise shrugged it off. She already had someone whod wanted to be her father. My dad was my dad, she said. I dont really need another one. OK, Ann thought, surprised. Thats that.

The first woman ever to give birth to a donor-conceived child never knew it. In 1884, an unscrupulous Philadelphia doctor named William Pancoast chloroformed one of his patients, then inseminated her using a rubber syringe loaded with sperm from what he considered his most attractive medical student. He eventually came clean to the womans husband, but the men agreed the mother would be better off left in the dark. The six medical students who witnessed the procedure were sworn to secrecy; however, compelled by the peculiar ethics of the case, one of them published an account of the affair 25 years later in a letter to the publication Medical World.

Donor insemination continued largely underground, sans chloroform, until the 1950s. Doctors typically used fresh semen from a limited supply of nearby medical studentsor occasionally their own. In 1953, an Arkansas doctoral student named Jerome K. Sherman successfully inseminated a woman with sperm hed frozen in solid carbon dioxide and preserved with glycerol. For the most part, a combination of stigma, religious opposition, and legal roadblocks kept the practice in the closet. In 1954 and again in 1963, state courts ruled that donor insemination constituted adultery, husband consent notwithstanding. They deemed the resulting children illegitimate.

That changed In 1973, when ULC, a nonprofit that drafts state legislation, introduced the Uniform Parentage Act, which was later adopted by a handful of states. It afforded legal paternity rights to the husbands of women who birthed children from donor sperm. A few years later, scientists developed reliable cryopreservation methods, setting the stage for commercial sperm banks. Freezing sperm allowed banks to stockpile catalogs of donors, ushering in an era of consumer choice.

Frozen sperm became standard in the late 1980s during the AIDS crisis, after several women contracted HIV from donors. A new infection could take months to show up on a test, so freezing kept sperm alive during a quarantine period, after which clinics could retest it. The practice remained voluntary, however; no law mandated it.

All the while, doctors advised couples against telling children the truth about their parentage, warning that it could threaten family unity. It wasnt until LGBTQ parents obtained widespread access to assisted reproduction that the practice started coming into the light. Nondisclosure wasnt really an option, and these children expressed curiosity about their origins.

The Sperm Bank of California, the countrys only nonprofit sperm bank, opened in Oakland in 1982, catering to lesbian couples. Responding to requests for more information, they pioneered the first identity disclosure program in 1983: Once donor-conceived people turned 18, they could request their donors identity and contact information. Commercial sperm banks seized the opportunity to expand their customer bases, adding their own identity disclosure programs.

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There's No Such Thing as Family Secrets in the Age of 23andMe - WIRED

'); $("#expandable-weather-block .modal-body #mrd-alert"+ alertCount).append(""+val.title+""); // if (window.location.hostname == "www.kmov.com" || window.location.hostname == "www.kctv5.com" || window.location.hostname == "www.azfamily.com" || window.location.hostname == "www.kptv.com" || window.location.hostname == "www.fox5vegas.com" || window.location.hostname == "www.wfsb.com") { if (val.poly != "" && val.polyimg != "") { $("#expandable-weather-block .modal-body #mrd-alert"+ alertCount).append('"+val.ihtml+""); $("#expandable-weather-block .weather-index-alerts").show(); $("#expandable-weather-block .modal-body h2").css({"font-family":"'Fira Sans', sans-serif", "font-weight":"500", "padding-bottom":"10px"}); $("#expandable-weather-block .modal-body p").css({"font-size":"14px", "line-height":"24px"}); $("#expandable-weather-block .modal-body span.wxalertnum").css({"float":"left", "width":"40px", "height":"40px", "color":"#ffffff", "line-height":"40px", "background-color":"#888888", "border-radius":"40px", "text-align":"center", "margin-right":"12px"}); $("#expandable-weather-block .modal-body b").css("font-size", "18px"); $("#expandable-weather-block .modal-body li").css({"font-size":"14px", "line-height":"18px", "margin-bottom":"10px"}); $("#expandable-weather-block .modal-body ul").css({"margin-bottom":"24px"}); $("#expandable-weather-block .modal-body pre").css({"margin-bottom":"24px"}); $("#expandable-weather-block .modal-body img").css({"width":"100%", "margin-bottom":"20px", "borderWidth":"1px", "border-style":"solid", "border-color":"#aaaaaa"}); $("#expandable-weather-block .modal-body #mrd-alert"+ alertCount).css({"borderWidth":"0", "border-bottom-width":"1px", "border-style":"dashed", "border-color":"#aaaaaa", "padding-bottom":"10px", "margin-bottom":"40px"}); }); } function parseAlertJSON(json) { console.log(json); alertCount = 0; if (Object.keys(json.alerts).length > 0) { $("#mrd-wx-alerts .modal-body ").empty(); } $.each(json.alerts, function(key, val) { alertCount++; $("#mrd-wx-alerts .alert_count").text(alertCount); $("#mrd-wx-alerts .modal-body ").append(''); $("#mrd-wx-alerts .modal-body #mrd-alert"+ alertCount).append(""+val.title+""); // if (window.location.hostname == "www.kmov.com" || window.location.hostname == "www.kctv5.com" || window.location.hostname == "www.azfamily.com" || window.location.hostname == "www.kptv.com" || window.location.hostname == "www.fox5vegas.com" || window.location.hostname == "www.wfsb.com") { if (val.poly != "" && val.polyimg != "") { $("#mrd-wx-alerts .modal-body #mrd-alert"+ alertCount).append(''); } else if (val.fips != "" && val.fipsimg != "") { // $("#mrd-wx-alerts .modal-body #mrd-alert"+ alertCount).append(''); } // } //val.instr = val.instr.replace(/[W_]+/g," "); $("#mrd-wx-alerts .modal-body #mrd-alert"+ alertCount).append(val.dhtml+"

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USA College of Medicine research examines novel genetic pathway that could treat COVID-19, new viral infections - FOX10 News

Five-year-old Abby Alvey of Richmond, who has Neimann-Pick disease, recently received a backyard playground through Make-A-Wish. Shes pictured with her grandmother, Patricia Savino; her parents, Melissa and Garland Alvey; and her older sister, Claire Alvey. Even with this medication, we dont know at any time when shell get worse. These could be the best years of her life, her dad said. My first thought what can we do to brighten her life a little bit? And of course, everyone thinks of Make-A-Wish.

When Evers Beck was 10, he was diagnosed with a brain tumor. Two years later, Make-A-Wish Greater Virginia sent him and his family to Japan, where they visited Mount Fuji, took sushi-making classes and traveled on the worlds fastest high-speed train.

When Evers Beck was 10, he was diagnosed with a brain tumor. Through Make-A-Wish Greater Virginia, he and his family were able to visit Japan. His mom, Joey Beck, said he loves Pokmon, sushi and anime, so Japan was the perfect trip.

Evers Beck, who traveled to Japan several years ago through Make-A-Wish Greater Virginia, is now a local Wish Ambassador.

When Evers Beck was 10 years old, he was diagnosed with a brain tumor and qualified for a wish through Make-A-Wish Greater Virginia.

Two years later, in 2017, he took a break from his chemotherapy treatments and boarded a plane to Japan.

I didnt really know much about Make-A-Wish other than what youd see on the news, said his mother, Joey Beck of Roanoke. So I was like, my sons not dying, were not applying.

But eventually the Beck family was persuaded. Beck said her son loves Pokmon, sushi and anime, so Japan was the perfect trip.

Evers is 15 now, and although the tumor is still there and is being monitored, he has been off of treatment for three years.

He had a huge boost and it was a nice break for us, for the whole family, his mother said.

But his wish trip wouldnt be possible today.

Make-A-Wish Greater Virginia has paused travel wishes, and anything else that involves a social gathering due to COVID-19 health concerns. The nonprofit organization, which serves critically ill children throughout the state except for counties and cities surrounding Washington, normally sees that about 80% of its wishes involve travel every year, said CEO Sheri Lambert.

Right now, none of those are being granted. Lambert said that families planning to go on trips have been asked to re-imagine their wishes.

The rest is here:

Make-A-Wish continues to bring kids hope during the pandemic - Roanoke Times

HERSHEY, Pa. A protein that is critical for retrovirus replication may select viral genetic material for packaging within the nuclei of host cells, rather than in the cytoplasm, as was previously believed. The research, led by a team at Penn State College of Medicine, could have implications for the development of therapeutics that target this protein.

Retroviruses are a type of virus that use cells asmachines to make more virus particles that are spread fromcell to cell. There are three major infectious human retroviruses, including human immunodeficiency virus-1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS). The lab of Dr. Leslie Parent, vice dean for research and graduate studies and professor of medicine, studies the avian retrovirus Rous sarcoma virus, which replicates similarly to HIV and causes tumors in domestic fowl.

Their research focuses on the role of a special protein called Gag that acts as an escort for genetic material in viral replication. It forms a complex by binding to the viral ribonucleic acid (RNA) to package it into an infectious virus particle. According to Parent, a professor of medicine and microbiology and immunology, their latest discovery puts scientists one step closer to developing therapeutics that can stop this complex from forming.

Our primary goal has been to understand where the initial interaction between the Gag protein and viral RNA occurs, said Parent. Other drugs and approaches have targeted viral replication after these complexes form. Our hope is that if we can better understand this interaction, early intervention strategies could be developed.

For years, scientists who studied retroviruses believed that Gag protein and viral RNA interacted only in the cytoplasm of the cell. But prior work by the Parent lab revealed that Gag proteins entered the nucleus of the cell as well. Based on that finding, they hypothesized that Gag protein might select viral RNA for packaging in the nucleus, where the RNA is made.

With so much activity going on in a cell, Parent and her colleagues put fluorescent "labels" on the Gag protein and viral RNA so they could watch their interactions in live cells using confocal microscopy. The images and videos of this process were captured and published with their data in mBio, a journal of The American Society for Microbiology.

As they hypothesized, they observed that Gag does bind viral RNA in the nucleus, and the complex traffics out of the nucleus. They propose that the viral Gag-RNA complex ultimately travels to the outer membrane of the cell where the viral particle is released to infect new cells. According to Parent, advances in technology have made this finding possible.

Visualizing a live cell in real time allows you see the intricate dynamics of its functions, Parent said. She noted the College of Medicines core facilities, including leading-edge live-cell microscopy, were integral to carrying out this project that has been years in the making. When you observe a cell over time, you can see the start, end and speed of various processes. It allows you to witness how a live cell deals with a viral infection.

Rebecca Kaddis Maldonado and Breanna Rice, postdoctoral scholars at the College of Medicine and coauthors on the publication, said knowing that Gag protein selects viral RNA in the nucleus opens up more questions that will be explored in future studies. They want to understand more about the kinetics of the interaction between Gag protein and viral RNA in the nucleus, mechanisms for how the complex moves outside the nucleus, and what other elements of the host cell may play a role in the process.

This observation is just the first of a series of investigations we need to carry out in order to understand this interaction, Maldonado said. The more we know about the details of this process, the better suited well be to propose or develop therapeutic targets.

Coauthors include Eunice Chen, Kevin Tuffy and Estelle Chiari of Penn State College of Medicine and Kelly Fahrbach and Thomas Hope of Northwestern University. Eunice Chen is a student in the College of Medicines MD/PhD Medical Scientist Training Program.

This research was supported by grants from the Pennsylvania Department of Health using Tobacco Settlement CURE Funds and the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the Pennsylvania Department of Health. The authors declare no conflict of interest.

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Caught in the act: Microscopy reveals key detail in retrovirus replication - Penn State News

SALT LAKE CITY, July 29, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, announced today that the company has launched its proprietary AMPLIFY technology, which further increases the performance of its Prequel noninvasive prenatal screening (NIPS) test. The proprietary AMPLIFY process increases the fetal fraction of a NIPS sample by preferentially sequencing the fetal cell-free DNA fragments that circulate in a mothers blood. AMPLIFY technology enables more accurate detection of fetal chromosome abnormalities. In the analytical validation involving samples from more than 1,000 pregnant women, fetal fraction is 2.3 times greater on average with AMPLIFY than with standard NIPS. This improvement reduces false positive and false negative resultsincluding for common aneuploidies, expanded aneuploidies, microdeletions and a babys sex. For instance, false negative performance in common aneuploidies improves 45x with AMPLIFY technology. Additionally, no samples powered by AMPLIFY technology had a fetal fraction below four percent. Other laboratories may fail samples with less than four percent fetal fraction.

Prequel already provided highly accurate results and this proprietary technology further increases the sensitivity of our test, said Nicole Lambert, president of Myriad International, Oncology and Womens Health. With AMPLIFY, Prequel maintains an industry-leading low rate of failed samplesdelivering results to 99.9 percent of patients. The important clinical benefits are that each woman who receives the test can expect highly accurate NIPS results, regardless of body mass index (BMI), race, or ethnicity.

Up to 50 percent of pregnant women present with high BMI to their healthcare provider. Studies have demonstrated that BMI is not evenly distributed across ethnicities, and up to 24 percent of women with high BMI will not receive a result on standard NIPS platforms due to low fetal fraction. Women who dont receive a result may do no further prenatal screening at all; they may go through subsequent rounds of NIPS, or they may undergo invasive procedures such as an amniocentesis or chorionic villus sampling, which can increase the risk of miscarriage and add unnecessary expense to the US healthcare system. Prequel with AMPLIFY technology overcomes the limitations of standard NIPS in order to provide equity of care to pregnant women.

About Prequel Prenatal ScreenThe Myriad Prequel Prenatal Screen is a non-invasive prenatal screen (NIPS) that uses cell-free DNA (cfDNA) to determine if a pregnancy is at an increased risk for chromosome abnormalities, such as Down syndrome. Compared to screening methods which use maternal age, ultrasound and serum screening, Prequel has been shown to be superior than by achieving a lower false-positive rate and false-negative rate than these other methods. Among other NIPS, Prequel has an industry leading test failure rate of 0.1 percent. The Prequel Prenatal Screen can be ordered with the Foresight Carrier Screen and offered to all women, including those with high body mass index, and ovum donor or a twin pregnancy.

About Myriad GeneticsMyriad Genetics Inc., is a leading personalized medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on three strategic imperatives: transitioning and expanding its hereditary cancer testing markets, diversifying its product portfolio through the introduction of new products and increasing the revenue contribution from international markets. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to launch of the Companys proprietary AMPLIFY technology; and the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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Myriad Launches Proprietary AMPLIFY Technology, Further Increasing the Performance of its Prequel NIPS Test - BioSpace

Angelman syndrome, a rare genetic condition, has been a central focus of UConn researcher Stormy Chamberlains career for over a decade. Since 2009, Chamberlain has been using induced pluripotent stem cells (iPSCs) in her lab at UConn Health to study human imprinting disorders that could lead to a cure.

Through a newly announced exclusive licensing agreement and research collaboration, Chamberlain and fellow UConn School of Medicine researcher Noelle Germain are now working with biopharmaceutical company Ovid Therapeutics Inc. on a promising genetic therapy.

Angelman syndrome affects approximately 1 in 12,000 to 1 in 20,000 people globally, and there are currently no approved therapies. People with Angelman syndrome experience developmental delays, have trouble walking or balancing, and are prone to seizures. They also have limited speech abilities, despite a tendency to laugh, smile, and have a happy demeanor. Individuals with Angelman syndrome typically have normal lifespans but are unable to live independently and require constant care from family or caregivers.

Current treatment options primarily consist of behavioral interventions and pharmacologic management of symptoms. Chamberlain and Ovid hope to provide more options to patients with Angelman through their strategic research collaboration.

Angelman syndrome occurs when a single gene inherited from a mothers 15th chromosome is deleted or inactive. The paternal copy of that gene, known as ubiquitin protein ligase E3A or UBE3A, is normally silenced in brain cells by UBE3A-antisense, a regulatory RNA.

Through the research collaboration and license agreement, Chamberlain, Germain, and Ovid will work to accelerate the development of a next-generation short hairpin RNA (shRNA)-based therapeutic for Angelman syndrome. An shRNA-based therapeutic may address the underlying genetic cause of Angelman syndrome by reducing the expression of UBE3A-antisense and restoring the function of UBE3A. This genetic approach may be used in combination with OV101 (gaboxadol), Ovids novel therapy. OV101 is currently in clinical development for the treatment of Angelman syndrome and Fragile X syndrome. Topline results in Angelman syndrome are expected at the end of 2020.

An shRNA therapeutic can target the genetic cause of Angelman syndrome at its source and may offer potential advantages to other next-generation approaches, says Chamberlain. Ovid is uniquely positioned to accelerate an shRNA therapeutic through late preclinical and clinical development, and our lab looks forward to working with the team at Ovid towards our common objective of impacting the lives of individuals living with Angelman syndrome and their families.

While Ovid and the UConn research team are hopeful that OV101 will serve as a core therapy for this Angelman syndrome, the collaboration will also grow the research pipeline for the future to ensure new therapies for individuals living with Angelman syndrome.

This collaboration was supported by UConns Technology Commercialization Services group through Amit Kumar, PhD. For more information about partnering with UConn and available technologies, visit innovation.uconn.edu.

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UConn Researchers Collaborate with Ovid Therapeutics on Genetic Therapy for Angelman Syndrome - UConn Today

Dr. Florence Haseltines resume is robust, if not intimidating: She has attended and taught at world-renowned universities, and received awards for championing womens health and advocating for womens rights. Most recently, she transformed the North Texas Genome Center at the University of Texas at Arlington into a COVID-19 testing facility for students.

Haseltine, 77, leveraged her personal connections, built on 27 years of working at the national level, to make sure that the center has the supplies necessary for testing. And that will promote her aspirations for the center: to study why the novel coronavirus appears to affect men more than women.

From a young age, she was determinedly curious about the differences between men and women. I kept asking my father, who was a scientist, why there are two sexes, and he tried hard to explain it, she said. I kept bugging him so much that finally one day he threw up his arms and said, When you grow up, you figure it out.

Haseltines career has centered on this question she asked her dad. After studying at the University of California at Berkeley and MIT, and getting her M.D. from the Albert Einstein College of Medicine, she trained as a reproductive endocrinologist and researched in vitro fertilization at Yale University. Her work helped couples struggling to have children. The Yale Fertility Center was one of the first clinics in the U.S. to offer in vitro fertilization.

In 1985, Haseltine became the Director of the Center for Population Research at the National Institute of Child Health and Human Development at the National Institutes of Health. Working there for nearly three decades, she helped increase federal funding for womens health research.

In 2018, a few years after Haseltines retirement, the president of UT-Arlington recruited her as a faculty member. The prospect of studying the human genome, or all of our genetic material, seemed like a perfect reason for her to return to academia.

Her career was influenced by her younger brother, William Haseltine. He developed some of the methodologies and technology used in genomics research as the founder of the biotechnology company Human Genome Sciences. It was clear if I was to make a second jump [in academia], it would be into the genome, she said.

When Haseltine first came to UT-Arlington, she planned to study why certain diseases affect men and women differently, and why, in some cases, one sex might suffer from more severe symptoms.

She thought that it might be due to differences between the sexes when it comes to some genetic information that determines our immune response. In particular, she wants to investigate a group of genes called human leukocyte antigens, or HLA.

HLA genes serve as an early warning for the immune system. These genes provide pieces of proteins made by foreign invaders, like a virus, to specialized immune cells that can then fight and eliminate the pathogen.

To proceed with the research, the North Texas Genome Center needed federal certification for processing human samples to diagnose, prevent and treat diseases. Last summer, Haseltine brought Anajane Smith, a researcher who studied HLA genes in Seattle, out of her own retirement to help the center get certified.

Haseltine knew Smith since the age of 6. They parted ways after college when she took a job on the East Coast and Smith took a position on the West Coast. Even after all this time, Smith jumped in to help when Haseltine needed her expertise.

With Smiths guidance, the North Texas Genome Centers officials got their required certification in January. Then the pandemic struck Texas and the university encouraged the centers director, Jon Weidanz, to shift the centers focus to testing for COVID-19.

Through personal relationships, Haseltine got the supplies necessary to test for SARS-CoV-2, the virus that causes COVID-19. She reached out to Dr. Mary Lake Polan, whom she had mentored at Yale University in 1975.

She has the ability to deal with people, so that, as focused as she is, she doesnt put them off, said Polan. They want to help her.

Polan is a board member of Quidel Corporation, a company that makes diagnostic healthcare products. Haseltine was able to get one of the companys SARS-CoV-2 assays or products that analyze COVID-19 tests the day that the assay was approved by the Food and Drug Administration.

Then she needed to make sure that the assays worked with the UT-Arlington centers equipment. She needed the genetic material, or the RNA, of SARS-CoV-2 to test the assays.

She contacted Scott Weaver, a colleague from the Global Virus Network, an international coalition of scientists dedicated to managing viral diseases.

Weaver, director of the Institute for Human Infections & Immunity at the University of Texas Medical Branch, gave Haseltine some SARS-CoV-2 RNA from the universitys World Reference Center on Emerging Viruses and Arboviruses.

With Haseltines help, staff at the North Texas Genome Center recently ran their first successful assays. Staff started processing tests from student athletes this month, and will continue to do so every four weeks thereafter. Other students can be tested after they return to campus if they show symptoms. And students will have no out-of-pocket costs for testing, according to a UT-Arlington spokesperson.

Haseltine now has the opportunity to join other members of the scientific community in studying why SARS-CoV-2 seems to affect men more than women. Haseltine and Weidanz have a hunch that certain forms of some HLA genes could offer a protective role against COVID-19 in women.

Science can be an incredibly competitive field. So the amount of cooperation by scientists to work together and fight COVID-19 stunned many, including Haseltine. Ive had a lot of people help me in my life, but Ive never seen this level of cooperation, she said. Everybody wants to do whatever they can.

Gina Mantica reports on science for The Dallas Morning News as part of a fellowship with the American Association for the Advancement of Science.

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How a renowned scientist used her personal network to transform UTA's North Texas Genome Center into a COVID-19 testing facility - The Dallas Morning...

A vaccine with the potential to be ready for distribution before the end of the year now moves into the final phase of testing, and Cincinnati is playing a key role in the research.The Moderna vaccine is being tested in the labs at the University of Cincinnati College of Medicine.We get to contribute to the solution and to have Cincinnati and our community to be involved in that is amazing, said UC College of Medicine faculty member Dr. Maggie Powers-Fletcher. Im thankful, and our study team is so grateful, to have this opportunity to participate.The Moderna study moved into phase three, which is when they inject about 30,000 people to see if the vaccine is effective and for how long.UC is one of about 100 testing laboratories across the nation involved in testing the vaccine for the Moderna study.Its very exciting. Were getting the ball rolling on a very important effort to learn more about the use and success of the vaccine against COVID-19, said Powers-Fletcher.This week, some sites are starting the first of two injections that will be given about a month apart. UC will begin their first injections in August.This is a unique vaccine in that its part of the genetic code, only a piece of the genetic code, that creates or prompts your body to make something that triggers your immune system, Powers-Fletcher said.The goal is to have a safe and effective vaccine ready before the end of 2020.The UC College of Medicine lab is within sight of the lab at Childrens Hospital where the Pfizer vaccine, which is also considered to be very promising, is being tested.Both studies are still looking for volunteers to participate in the research. To sign up for the UC Moderna study, click here or call 513-245-3417.To sign up for the Children's Pfizer study, email gambleprogram@cchmc.org or call 513-636-7699.

A vaccine with the potential to be ready for distribution before the end of the year now moves into the final phase of testing, and Cincinnati is playing a key role in the research.

The Moderna vaccine is being tested in the labs at the University of Cincinnati College of Medicine.

We get to contribute to the solution and to have Cincinnati and our community to be involved in that is amazing, said UC College of Medicine faculty member Dr. Maggie Powers-Fletcher. Im thankful, and our study team is so grateful, to have this opportunity to participate.

The Moderna study moved into phase three, which is when they inject about 30,000 people to see if the vaccine is effective and for how long.

UC is one of about 100 testing laboratories across the nation involved in testing the vaccine for the Moderna study.

Its very exciting. Were getting the ball rolling on a very important effort to learn more about the use and success of the vaccine against COVID-19, said Powers-Fletcher.

This week, some sites are starting the first of two injections that will be given about a month apart. UC will begin their first injections in August.

This is a unique vaccine in that its part of the genetic code, only a piece of the genetic code, that creates or prompts your body to make something that triggers your immune system, Powers-Fletcher said.

The goal is to have a safe and effective vaccine ready before the end of 2020.

The UC College of Medicine lab is within sight of the lab at Childrens Hospital where the Pfizer vaccine, which is also considered to be very promising, is being tested.

Both studies are still looking for volunteers to participate in the research.

To sign up for the UC Moderna study, click here or call 513-245-3417.

To sign up for the Children's Pfizer study, email gambleprogram@cchmc.org or call 513-636-7699.

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Cincinnati is key in hope for COVID-19 vaccine before the end of 2020 - WLWT Cincinnati

July 28, 2020 -Community-based genetic screening could enhance population health by identifying individuals at high risk for three inherited conditions known to cause cancer and increased risk for heart attack and stroke, a study published in Nature Medicine revealed.

Three inherited genetic conditions breast and ovarian cancer, Lynch syndrome, and familial hypercholesterolemia are termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, researchers noted. For these conditions, early identification and intervention can have a meaningful impact on clinical actionability and public health.

Researchers behind the Healthy Nevada Project, a community-based population health study combining genetic, clinical, environmental, and social data, started notifying consenting participants who have certain genetic variants that predispose them to CDCT1 genetic conditions.

Initial results from nearly 27,000 participants showed that 90 percent of carriers of the CDCT1 genetic conditions were not previously identified in a clinical setting. This finding supports the use of population genetic screening to identify at-risk carriers not identified during routine care.

Our first goal was to deliver actionable health data back to the participants of the study and understand whether or not broad population screening of CDC Tier 1 genomic conditions was a practical tool to identify at-risk individuals, said Joseph Grzymski, PhD, the principal investigator of the Healthy Nevada Project, a research professor at the Desert Research Institute (DRI), chief scientific officer for Renown Health and lead author of the study.

Now, two years into doing that, it is clear that the clinical guidelines for detecting risk in individuals are too narrow and miss too many at-risk individuals.

Within the group of 26,906 participants the researchers studied, 358 (1.33 percent) were genetic carriers for CDCT1 genetic conditions. However, only 25 percent of those individuals met clinical guidelines for genetic screening. Additionally, more than 20 percent of the carriers already had a diagnosis of disease relevant to their underlying genetic condition.

Were at a point now where its possible to do clinical-grade genetic screening at population-scale, said James Lu, M.D. PhD, co-founder and chief scientific officer of Helix and senior co-author of the study.

What this study demonstrates is the potential impact of doing so. By making genetic screening available more broadly, we can help the millions of Americans who are unaware that they are living at increased risk for highly actionable, genetic conditions take action.

Most significantly, the researchers found that of the 273 participants who were carriers of the CDCT1 genetic conditions and had clinical record information, only 22 individuals showed any previous suspicion of their underlying genetic conditions.

For the first time, we are providing information at the individual level so study participants can make lifesaving changes to reduce their risk based on their genetics, said Anthony Slonim, MD, DrPH, FACHE, president and CEO of Renown Health and co-director of the Project study.

Were conducting research on the community level to develop leading-edge research on health determinants for entire neighborhoods, states and eventually, the country. Returning these results allows us to understand the prevalence of genetically programmed diseases and illnesses that we have here in Nevada and ensure we are providing the best prevention and care plans. For the individual, the return of results can be lifechanging.

Launched in 2018, the Healthy Nevada Project is a collaboration between Renown Health and Desert Research Institute (DRI). Recently, the initiative began incorporating COVID-19 data from consenting participants. Using the studys online survey tools, a population health research team asked participants about their COVID-19 experiences.

In a 13-question online survey, researchers asked participants about possible exposure or risks of COVID-19, such as recent travel, attendance at large public events, and whether individuals have experienced symptoms of the virus.

We've had over 14,000 participants respond as of Monday, said Joseph Grzymski, PhD, an associate research professor at the Desert Research Institute (DRI), Chief Science Officer for Renown Health, and principal investigator of the Healthy Nevada Project.

The data that our participants have provided us, in less than a week, has allowed us to discover risk factors within communities and take action to live longer, healthier lives. That's what makes the Healthy Nevada Project so exciting for all of us.

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Community-Based Genetic Screening Could Boost Population Health - HealthITAnalytics.com

The American Heart Association has developed guidelines for cardiovascular practitioners who may be looking to incorporate genetic testing into the care of patients with inherited cardiovascular diseases.

In a scientific statement published in the journal Circulation: Genomic and Precision Medicine on Thursday, researchers and clinicians on behalf of the American Heart Association Council on Genomic and Precision Medicine; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; and the Council on Clinical Cardiology said that genetic testing could be useful in the management of a variety of cardiovascular conditions, including cardiomyopathies, arrhythmic disorders, thoracic aortic aneurysms and dissections, and familial hypercholesterolemia (FH).

However, not all cardiovascular practitioners are fully aware of the utility and challenges of incorporating genetic test results into the care of patients and their families, the authors noted. The statement they released summarized current best practices with respect to genetic testing and its implications for the management of these diseases.

For example, the authors wrote, "Genetic testing typically should be reserved for patients with a confirmed or suspected diagnosis of an inherited cardiovascular disease, or for individuals at high a priori risk resulting from a previously identified pathogenic variant in their family." This involves rigorous, disease-appropriate phenotyping, and a comprehensive family history that spans at least three generations. If these two elements together establish or strongly suggest an inherited cardiovascular disease, then the next step is to identify the most appropriate person for genetic testing.

Next, the authors said, if the decision is made to proceed with genetic testing, the clinician should decide what scope of genetic testing should be performed. The choice of testing ranges from targeted sequencing of a single gene or a few genes most likely to be involved in the disease, to large gene panels that include limited-evidence genes, to unbiased exome or genome sequencing that queries all genes. While a clinician's inclination might be to test all genes possible, this may not increase the likelihood of clinically actionable results in adult patients, the authors noted.

Further, expanded test panels may increase the number of variants of uncertain significance (VUS) that are identified. And in the case of exome or genome sequencing, expanded testing may increase the chance of picking up secondary or incidental findings that are not relevant to the disease in question, which can lead to confusion.

"Providers should also be aware that genetic testing might not reveal a cause or confirm a diagnosis of the patient's disease because the yield of genetic testing for any inherited cardiovascular disease remains less than 100%, usually much less than 100%," the authors wrote.

If testing is performed, the experts said, clinicians must also be aware of how they plan to return results to patients. This should be done in the presence of a genetic counselor, so that the patient has a full understanding of the implications of the results for their health.

The authors also noted the possibility for secondary or incidental findings from genetic testing. Secondary or incidental findings are becoming particularly relevant because patients are increasingly undergoing genetic testing with exome or genome sequencing in order to maximize the chance of identifying causal pathogenic variants and because costs between gene panels and exomes or genomes are narrowing.

The current recommendation is that patients should be notified of pathogenic or likely pathogenic variants in any of the 59 genes deemed medically actionable by the ACMG, if they have not opted out of receiving these results, the AHA experts said. However, VUS are not typically returned when discovered as incidental findings. Importantly, 30 of the ACMG 59 genes are related to cardiovascular diseases.

"The field of clinical genetics is in rapid flux. We anticipate that this scientific statement will need to be updated to reflect new advances in the field and new disease-specific guidelines, expert consensus documents, and other statements that are published," the authors wrote. "Reliable classification of variants identified in genetic testing will remain a preeminent challenge for the practice of clinical genetics. Ongoing efforts by ClinGen to refine gene-specific variant classification criteria will be critical, as will laboratory-based functional platforms to reliably interpret variants in a medium-throughput or high-throughput fashion."

This story first appeared in our sister publication, Genomeweb.

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American Heart Association sets genetic testing guidelines for cardiovascular disease - ModernHealthcare.com

PHOENIX and SAN FRANCISCO, July 28, 2020 (GLOBE NEWSWIRE) -- Ivy Brain Tumor Center at Barrow Neurological Institute announced today that the first patient has been dosed in an investigator-initiated Phase 0/2 clinical trial of infigratinib in recurrent high-grade glioma driven by FGFR genetic alterations. Infigratinib is an investigational, orally administered, FGFR1-3 selective tyrosine kinase inhibitor being developed by BridgeBio Pharma, Inc. (Nasdaq: BBIO) affiliate company QED Therapeutics, Inc.

The investigator-initiated Phase 0/2 trial is designed to confirm drug effects within days of exposure, and only to continue dosing when the drug is active in a patients own tumor. The primary objective of the Phase 0 arm is to assess how effectively infigratinib can cross the blood-brain barrier the most significant obstacle to developing new, effective therapies for aggressive brain tumors like glioblastoma. Patients with successful tumor penetration will receive infigratinib long-term in a Phase 2 expansion arm of the trial. The primary endpoint of the expansion phase is progression-free survival rate at six months. The study will also measure how well infigratinib is impacting its molecular target in each patients tumor.

FGFR (fibroblast growth factor receptor) genetic alterations have been shown to spur growth in malignant tumors. Five to seven percent of glioblastoma patients tumors are driven by FGFR signaling. During the trial screening process, the patients tumor tissue from prior surgery will be tested for the FGFR-TACC3 fusion gene or mutations in FGFR1 and FGFR3 genes. Patients with tumors that have these fusions or mutations are eligible for this study.

In the preclinical studies, our pharmacokinetics program at the Ivy Brain Tumor Center tested seven FGFR inhibitors for their ability to cross the blood-brain barrier. Infigratinib was one of the most promising agents, said Shwetal Mehta, Ph.D., deputy director of the Ivy Brain Tumor Center.

Infigratinib was previously tested in an uncontrolled Phase 2 study for recurrent high-grade gliomas, said Nader Sanai, M.D., director of the Ivy Brain Tumor Center. The results were intriguing, but inconclusive. This Ivy Phase 0/2 trial seeks to provide direct biological evidence of drug effects in individual patients, allowing us to understand which glioblastoma patients may benefit from infigratinib.

The launch of this investigator-initiated trial is an exciting step in the study of infigratinib for patients with recurrent, high-grade glioma, said Susan Moran, M.D., M.S.C.E., chief medical officer of QED Therapeutics. We anticipate this study being conducted by the Ivy Center will generate valuable information on the ability of infigratinib to reach brain tumors, which is a critical first step in evaluating whether infigratinib, alone or in combination, could potentially provide a therapeutic option for patients with this dire disease.

For additional information on this Phase 0/2 trial in recurrent high-grade glioma, including eligibility criteria, visit http://www.clinicaltrials.gov/ct2/show/NCT04424966.

About Ivy Brain Tumor Center

Ivy Brain Tumor Center at the Barrow Neurological Institute in Phoenix, AZ is a non-profit translational research program that employs a bold, early-phase clinical trials strategy to identify new treatments for aggressive brain tumors, including glioblastoma. The Ivy Centers Phase 0 clinical trials program is the largest of its kind in the world and enables personalized care in a fraction of the time and cost associated with traditional drug development. Unlike conventional clinical trials focusing on single drugs, its accelerated trials program tests therapeutic combinations matched to individual patients. Learn more at IvyBrainTumorCenter.org. Follow the Ivy Brain Tumor Center on Facebook, Instagram, Twitter and LinkedIn.

About QED Therapeutics, Inc.

QED Therapeutics, an affiliate of BridgeBio Pharma, Inc. is a biotechnology company focused on precision medicine for FGFR-driven diseases. Our lead investigational candidate is infigratinib (BGJ398), an orally administered, FGFR1-3 selective tyrosine kinase inhibitor that has shown activity that we believe to be meaningful in clinical measures, such as overall response rate, in patients with chemotherapy-refractory cholangiocarcinoma with FGFR2 fusions and advanced urothelial carcinoma with FGFR3 genomic alterations. QED intends to submit a New Drug Application (NDA) with the United States Food and Drug Administration for second and later-line cholangiocarcinoma in 2020. QED Therapeutics is also evaluating infigratinib in clinical studies for the treatment of achondroplasia. We plan to conduct further clinical trials to evaluate the potential for infigratinib to treat patients with other FGFR-driven tumor types and rare disorders.

For more information on QED Therapeutics, please visit the Company's website at http://www.qedtx.com.

About BridgeBio Pharma, Inc.

BridgeBio is a team of experienced drug discoverers, developers and innovators working to create life-altering medicines that target well-characterized genetic diseases at their source. BridgeBio was founded in 2015 to identify and advance transformative medicines to treat patients who suffer from Mendelian diseases, which are diseases that arise from defects in a single gene, and cancers with clear genetic drivers. BridgeBios pipeline of over 20 development programs includes product candidates ranging from early discovery to late-stage development. For more information visit bridgebio.com

BridgeBio Pharma Forward Looking Statements

This press release contains forward-looking statements. All statements contained herein other than statements of historical fact constitute forward-looking statements, including statements relating to expectations, plans, and prospects regarding QED Therapeutics clinical development plans, clinical trial results, timing, completion and outcomes of clinical trials, including this investigator-initiated trial, the competitive environment, the success of QED Therapeutics collaboration with the Ivy Brain Tumor Center and its impact on QED Therapeutics clinical development strategy, and the clinical and therapeutic potential of infigratinib. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to, QED Therapeutics ability to initiate and continue its planned clinical trials of infigratinib, its ability to advance infigratinib in clinical development, the timing and success of any such continued clinical development, and the Ivy Brain Tumor Centers ability to initiate and enroll its investigator-initiated clinical trial of infigratinib and the nature of QEDs interactions with regulatory authorities. Moreover, QED Therapeutics operates in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of QED Therapeutics management as of the date of this release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. All forward-looking statements in this press release are based on information available to QED Therapeutics as of the date hereof, and QED Therapeutics disclaims any obligation to update these forward-looking statements.

MEDIA:Ivy Brain Tumor CenterMelinda LangdonDirector, Marketing and Communications(623) 297-1317melinda.langdon@ivybraintumorcenter.org

QED Therapeutics Ian StoneCanale Communications619-849-5388ian@canalecomm.com

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Ivy Brain Tumor Center and BridgeBio Pharma's QED Therapeutics Announce Dosing of First Patient in Investigator-Initiated Phase 0/2 Clinical Trial of...

CAMBRIDGE, Mass. and NEW YORK, July 28, 2020 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, tumor-agnostic therapies, today announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric human epidermal growth factor receptor 2 (HER2) mutation or an epidermal growth factor receptor (EGFR) or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options. BDTX-189, an orally available, irreversible small molecule inhibitor, is the Companys lead product candidate designed to selectively inhibit the activity of a broad range of previously unaddressed oncogenic driver mutations of the ErbB kinases in EGFR and HER2.

While targeted therapies, such as kinase inhibitors, have transformed the treatment of cancer, only a small percentage of patients with metastatic cancer have tumors with genetic profiles that could make them eligible for an approved precision oncology medicine. The FDAs decision to grant Fast Track designation is an important recognition of BDTX-189s potential to treat patients with currently unaddressed oncogenic mutations in EGFR and HER2, said David M. Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. We look forward to working closely with the FDA as we continue to enroll and dose patients in the MasterKey-01 trial, our Phase 1/2 clinical study of BDTX-189, as part of our mission to discover and develop novel, tumor-agnostic, precision oncology therapies for genetically defined cancers.

The FDA's Fast Track designation provides the potential for an expedited review of new product candidates intended to treat serious or life-threatening conditions with high unmet need, allowing important new drugs to become available more quickly to patients suffering from these conditions.Benefits of Fast Track designation include enhanced interaction with the FDA, as well as potential eligibility to obtain accelerated approval and priority review at the time of a New Drug Application (NDA) filing if relevant criteria are met. More information about FDA Fast Track designation can be found at http://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/fast-track.

About MasterKey-01

MasterKey-01 (NCT04209465) is a combined Phase 1/2 open-label, two-part, multicenter study to assess the safety, tolerability, pharmacokinetics, and anti-tumor activity of BDTX-189, in adult patients with advanced solid tumors who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. Part A is a Phase 1, first-in-human, open-label dose escalation study, comprised of initial single-patient, accelerated titration cohorts followed by multiple-patient cohorts utilizing a Bayesian design. Part A is designed to determine the recommended Phase 2 dose and schedule in up to 88 patients with allosteric human epidermal growth factor receptor 2 (HER2) or HER3 mutation; epidermal growth factor receptor (EGFR) or HER2 exon 20 insertion mutation; HER2 amplified or overexpressing tumor; or, EGFR exon 19 deletion or L858R mutation. Part B is a Phase 2, open-label, multicenter basket study designed to determine antitumor activity and safety in adult patients with solid tumors that have an allosteric HER2 mutation or EGFR or HER2 exon 20 insertion mutations using next-generation sequencing. This part will utilize a Simon 2-stage design and enroll up to 100 patients in four cohorts: 1) non-small cell lung cancer with EGFR or HER2 exon 20 insertion mutations; 2) breast cancer with an allosteric ErbB mutation; 3) solid tumors (except breast) with S310F/Y mutation; and, 4) other tumors harboring allosteric ErbB mutations not included in cohorts 1-3.

About BDTX-189

BDTX-189 is an orally available, irreversible small molecule inhibitor that is designed to block the function of an undrugged family of oncogenic proteins defined by driver mutations across a range of tumor types, and which affect both of the epidermal growth factor receptor (EGFR) and the tyrosine-protein kinase, ErbB-2, or human epidermal growth factor receptor 2 (HER2). These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain exon 20 insertions, and additional activating oncogenic drivers of ErbB. The ErbB receptors are a group of receptor tyrosine kinases involved in key cellular functions, including cell growth and survival. BDTX-189 is also designed to spare normal, or wild type EGFR, which we believe has the potential to improve upon the toxicity profiles of current ErbB kinase inhibitors.

Currently, there are no medicines approved by the U.S. Food and Drug Administration to target all of these oncogenic mutations with a single therapy.

About Black Diamond

Black Diamond Therapeutics is a precision oncology medicine company pioneering the discovery of small molecule, tumor-agnostic therapies. Black Diamond targets undrugged mutations in patients with genetically defined cancers. Black Diamond is built upon a deep understanding of cancer genetics, protein structure and function, and medicinal chemistry. The Companys proprietary technology platform, Mutation-Allostery-Pharmacology (MAP) platform, is designed to allow Black Diamond to analyze population-level genetic sequencing data to identify oncogenic mutations that promote cancer across tumor types, group these mutations into families, and develop a single small molecule therapy in a tumor-agnostic manner that targets a specific family of mutations. Black Diamond was founded by David M. Epstein, Ph.D. and Elizabeth Buck, Ph.D., and, beginning in 2017, together with Versant Ventures, began building the MAP platform and chemistry discovery engine.For more information, please visit http://www.blackdiamondtherapeutics.com.

Forward-Looking Statements

Statements contained in this press release regarding matters that are not historical facts are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the potential of Fast Track designation to accelerate development and approval of BDTX-189, the Companys future plans or expectations for BDTX-189, including expectations regarding the success of its current clinical trial for BDTX-189 and future plans or expectations for the Mutation-Allostery-Pharmacology platform. Any forward-looking statements in this statement are based on managements current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: the success, cost, and timing of the Companys product candidate development activities and planned clinical trials, the Companys ability to execute on its strategy, regulatory developments in the United States, the Companys ability to fund operations, and the impact that the current COVID-19 pandemic will have on the Companys clinical trials, supply chain, and operations, as well as those risks and uncertainties set forth in its 2019 annual report on Form 10-K filed with the United States Securities and Exchange Commission and its other filings filed with the United States Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Contacts:

For Investors:Natalie Wildenradtinvestors@bdtherapeutics.com

For Media:Kathy Vincent(310) 403-8951media@bdtherapeutics.com

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Black Diamond Therapeutics Granted Fast Track Designation by the FDA for BDTX-189 for the Treatment of Adult Patients with a Solid Tumor Harboring an...

When someone is diagnosed with cancer especially a particularly difficult kind like pancreatic cancer they often look for the best.

The best treatment. The best doctor. The best hospital. The best chance.

When it comes to pancreatic cancer, the best healthcare team is:

And if you are considering or getting surgery, the Pancreatic Cancer Action Network (PanCAN) recommends seeing a surgeon who performs more than 15 pancreatic surgeries per year to determine your eligibility and to perform the surgery.

If you have a rare form of pancreatic cancer (any type other than pancreatic adenocarcinoma), it is also important to see a doctor who has experience treating your specific type of cancer, if possible.

When trying to find the best doctors and center for you, it is important to consider finances and insurance coverage, whether you are able to travel, what type of pancreatic cancer you have, what your treatment goals are and what you are looking for in a healthcare team.

PanCAN keeps a list of pancreatic cancer specialists and high-volume centers throughout the country. Contact our Patient Services for specialists that meet your needs, such as expertise and geography.

Pancreatic cancer is relatively rare, and its treatment requires specialized knowledge and experience. While local hospitals can offer quality care, large academic cancer centers may be more likely to have doctors who are up to date on pancreatic cancer treatments and research.

These centers are also more likely to offer more clinical trials, a multidisciplinary team and support services than smaller, local hospitals.

Its important to remember that every patient is different, has different needs and responds to treatment differently.

Precision medicine treatment based on a persons or their tumors biology may help find the treatment that is best for you. PanCANs Know Your Tumor precision medicine service can help eligible patients access tumor biomarker testing and genetic testing to tell you about your biology and inform treatment decisions, regardless of where you are being treated. Contact PanCANs Patient Services for more information about precision medicine and Know Your Tumor.

When considering a doctor, ask:

Remember that your healthcare team is made up of more than just your doctor, and all roles are critical. For example, PanCAN recommends patients see a registered dietitian who has experience working with cancer patients. This person may be a part of your doctors or institutions care team, or they may be found outside of it.

No matter what, be sure to ask any current or prospective healthcare team members questions. Its important that you feel comfortable and supported by your healthcare team.

During the coronavirus pandemic, you may have additional challenges finding a doctor. Hospitals and institutions all have different policies right now. If the doctor or institution you are working with or want to see is not providing what you need, contact Patient Services. Our team can help you figure out other options, including helping you find another specialist or treatment center if needed.

And right now, advocating for yourself is more critical than ever. PanCAN is always here to support you in that endeavor and with anything else you may need.

Follow this link:

Choosing the Best Pancreatic Cancer Doctor and Hospital for You - Pancreatic Cancer News & Stories

Genetic testing may be a helpful tool in diagnosing autism and intellectual disability, but published data does not adequately support its use as a standard predictor of antidepressant response, James B. Potash, MD, MPH, said during a session at the virtual 2020 Psych Congress Elevateconference on the role of genetic testing in psychiatry.

There is ample reason to think that genetic variation ought to predict antidepressant response but research has shown mixed results, said Dr. Potash, who is the Henry Phipps Professor, Director and Psychiatrist-in-Chief, at Johns Hopkins Medicine, Baltimore, Maryland, and has been working in the field of genetics of mood disorders for more than 20 years.

Dr. Potash is a member of the American Psychiatric Association Council on Research, which had a task force analyze the issue in recent years. In a systematic review of pharmacogenetic tests of antidepressants, the task force found that the quality of the data provided by the tests on pharmacodynamicshow a drug affects the brainwas low, he said. However, the study, published in The American Journal of Psychiatry, found the tests provided higher-quality data on regarding particular genes related to how a drug is metabolized in the liver.

Their conclusion was at present there are insufficient data to support the widespread use of combinatorial pharmacogenetic testing in clinical practice, although there are clinical situations in which the technology may be informative, particularly in predicting side effects, Dr. Potash explained.

Similarly, an International Society of Psychiatric Genetics committee on genetic testing last year reached the conclusion that evidence to support widespread use of pharmacogenetic tests is inconclusive. But the statement also says when pharmacogenetic testing results are already available, providers are encouraged to integrate this information into their medication selection and dosing decisions, he said.

As for the future direction of genetic testing in psychiatry, Dr. Potash said there is ongoing research into its use in bipolar disorder.

A study involving 2500 people with bipolar disorder, published in Lancet by the International Consortium on Lithium Genetics, found some genetic variations were statistically significantly associated with response to lithium treatment. People with the highest Polygenic Risk Score (PRS) for schizophrenia had the lowest response to lithium treatment, and people with the lowest schizophrenia PRS had the highest response to lithium treatment. In addition, a paper recently published in Molecular Psychiatry found that people with bipolar disorder who had the lowest PRS for depression were 75% more likely to respond favorably to lithium, compared with those with the highest depression PRS scores.

Dr. Potash also spoke about the importance of a more traditional genetic research tool: collecting a detailed family history from a patient.

It has been known for a long time but its not always implemented, he said, noting that familial recurrence risk has been analyzed for more than 100 years.

For example, he explained, if one parent has schizophrenia and no siblings or second-degree relatives do, a child has a 6% risk of developing schizophrenia. But if one parent, two siblings, and a second-degree have the disorder, the relative the risk of a child inheriting it is 36%.

That kind of information is important, he said. Very important. Its valuable.

Terri Airov

References

Amare AT, Schubert KO, Hou L.,et al.Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.Molecular Psychiatry. 2020 March 16;[Epub ahead of print].

Genetic Testing Statement. International Society of Psychiatric Genetics. Accessed July 15, 2020.

Hou L, Heilbronner U, Degenhardt F, et al. Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet. 2016;387(10023):1085-1093.

The role of genetic testing in psychiatry. Presented at Psych Congress Elevate: Virtual; July 26, 2020.

Zeier Z, Carpenter LL, Kalin NH, et al. Clinical implementation of pharmacogenetic decision support tools for antidepressant drug prescribing. The American Journal of Psychiatry. 2018;175:873886.

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The Limitations and Promise of Genetic Testing in Psychiatry - Psych Congress Network

NEWPORT BEACH, Calif.--(BUSINESS WIRE)--jCyte Inc., a biotech company dedicated to preserving and restoring vision in patients with retinitis pigmentosa and other degenerative retinal disorders, announced today promising results from a Phase 2b clinical trial of jCell in retinitis pigmentosa (RP), an inherited retinal disease, irrespective of genetic subtype.

jCell is a first-in-class investigational treatment for RP which has received FDA Regenerative Medicine Advanced Therapy (RMAT) designation. In addition to RMAT, jCell has received Orphan Drug designation from the FDA and the European Medicines Agency (EMA).

The Phase 2b trial was a multicenter, randomized study that evaluated the safety and efficacy of intravitreal injection of jCell therapy in adult subjects with RP. A large and broad set of patients with RP with best-corrected visual acuity (BCVA) between 20/80 and 20/800 were randomized to treatment versus sham. Treatment consisted of a single intravitreal injection of either 3 or 6 million human retinal progenitor cells (hRPC). The study evaluated changes in visual function and functional vision in subjects with RP who received a single jCell injection in comparison to a sham-treated control group.

The primary endpoint in the Phase 2b study was mean change in best corrected visual acuity (BCVA) from baseline to month 12. Secondary endpoints included low light mobility, contrast sensitivity, kinetic visual fields, and a visual function questionnaire. In a post hoc exploratory analysis, the primary and secondary endpoints were assessed in a target subgroup of patients meeting the following criteria: 1) study eye with reliable fixation (12 central diameter and/or steady central fixation) and 2) study eye did not have significantly worse BCVA than the fellow eye (15 letters).

The Phase 2b clinical trial was specifically designed to learn more about the clinical effects of jCell therapy in a broad set of patients suffering from RP to better understand three critical study variables: the optimal jCell dose, the performance of clinical trial endpoints in the study population and the RP patient population likely to realize the most pronounced improvement from a single jCell treatment during the 12-month pivotal trial study period.

Phase 2b Results

A total of 84 patients were randomized of which 74 met criteria for the per protocol analysis. The mean change in BCVA from baseline to month 12 were +2.81, +2.96, and +7.43 letters in the sham (N=26), 3.0x106 hRPC (N=25), and 6.0x106 hRPC (N=23) treatment arms, respectively. In a post hoc exploratory analysis of the target subgroup (n=37), mean change in BCVA from baseline to month 12 were +1.85, -0.15, and +16.27 letters in the sham (N=13), 3.0x106 hRPC (N=13), and 6.0x106 hRPC (N=11) treatment arms, respectively (p=0.003 for 6.0x106 hRPC vs sham). Supportive improvements in the 6.0x106 hRPC target subgroup compared to the control (sham) group were also observed in all secondary endpoints which further support the BCVA findings in this subpopulation. Adverse events were generally minor and transient; there was one serious adverse event in the 3.0x106 hRPC arm of Grade 3 ocular hypertension that resolved with treatment, but no serious adverse events nor any adverse events greater than Grade 1 (mild) in the higher, 6 million cell treatment group during the 12-month study period that were related to the study treatment.

Based on these results, the company plans to advance jCell into a pivotal trial utilizing the data generated, which is supportive of both the efficacy and safety of jCell therapy in a broad set of RP patients. The Phase 2b study also provides essential insights into the three critical study variables which are key to optimizing the probability of technical success of the upcoming jCell pivotal trial.

There is currently no effective treatment for RP, and once photoreceptors are lost, they do not regenerate. The promising results from this Phase 2b study suggest that jCell therapy in patients with RP can result in significant slowing of visual deterioration and an improvement in function of existing photoreceptors. The primary goal of jCell therapy is to preserve, and potentially improve vision by intervening in the disease process at a time when dystrophic photoreceptors can be protected and reactivated. We are excited to be continuing the development of jCell investigational therapy, based on these promising Phase 2b results, for patients with this degenerative retinal disease, said Anthony Joseph, M.D., Ophthalmic Consultants of Boston, who presented the Phase 2b data at the ASRS meeting.

We are thrilled to report these encouraging Phase 2b results from one of the largest studies ever conducted in RP, which indicate significant clinical activity of jCell in patients agnostic of genetic subtype, said Paul Bresge, Chief Executive Officer, jCyte, Inc. The Phase 2b results reported that jCell therapy had promising efficacy and was well tolerated in patients, and we plan to advance jCell into a pivotal clinical trial in 2021. There is currently no FDA approved treatment option for RP patients, irrespective of genetic subtype. We believe jCell has the potential to be the first approved therapy to address this critical unmet medical need, and dramatically improve the lives of patients with this progressive, blinding disease which typically presents early in the lives of the approximately 1:3500 people who are affected.

About Retinitis Pigmentosa (RP)

Retinitis pigmentosa (RP) is a rare, genetic condition that progressively destroys the rod and cone photoreceptors in the retina. It often strikes people in their teens, with many patients rendered legally blind by middle age. Worldwide, an estimated 1.9 million people suffer from the disease, including approximately 100,000 people in the U.S., making it the leading cause of inheritable blindness.

About jCyte, Inc.

jCyte, Inc. is a clinical-stage biotech company focused on developing jCell therapy for retinitis pigmentosa (RP) and other degenerative retinal disorders. jCell is a first-in-class investigational treatment for retinitis pigmentosa, an inherited retinal disease. The treatment is minimally-invasive and given as an intravitreal injection. There are currently no FDA approved therapies for RP agnostic of genetic subtype. The company is pioneering a new era of regenerative therapies to treat patients with unmet medical needs. For more information, visit http://www.jcyte.com

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jCyte Inc. Announces Promising Phase 2b Results of jCell Therapy in Retinitis Pigmentosa - Business Wire

Newswise Irvine, CA July 27, 2020 In a new study, researchers found that night- versus day-biting species of mosquitoes are behaviorally attracted and repelled by different colors of light at different times of day. Mosquitoes are among major disease vectors impacting humans and animals around the world and the findings have important implications for using light to control them.

The University of California, Irvine School of Medicine-led team studied mosquito species that bite in the daytime (Aedes aegypti, aka the Yellow Fever mosquito) and those that bite at night (Anopheles coluzzi, a member of the Anopheles gambiae family, the major vector for malaria). They found distinct responses to ultraviolet light and other colors of light between the two species. Researchers also found light preference is dependent on the mosquitos sex and species, the time of day and the color of the light.

Conventional wisdom has been that insects are non-specifically attracted to ultraviolet light, hence the widespread use of ultraviolet light bug zappers for insect control. We find that day-biting mosquitoes are attracted to a wide range of light spectra during the daytime, whereas night-biting mosquitoes are strongly photophobic to short-wavelength light during the daytime, said principal investigator Todd C. Holmes, PhD, a professor in the Department of Physiology and Biophysics at the UCI School of Medicine. Our results show that timing and light spectra are critical for species-specific light control of harmful mosquitoes.

The new study titled, Circadian Regulation of Light-Evoked Attraction and Avoidance Behaviors in Daytime- versus Nighttime-Biting Mosquitoes, is published in Current Biology. Lisa S. Baik, a UCI School of Medicine graduate student researcher who recently completed her PhD work, is first author.

Mosquitoes pose widespread threats to humans and other animals as disease vectors. It is estimated historically that diseases spread by mosquitoes have contributed to the deaths of half of all humans ever to have lived. The new work shows that day-biting mosquitoes, particularly females that require blood meals for their fertilized eggs, are attracted to light during the day regardless of spectra. In contrast, night-biting mosquitoes specifically avoid ultraviolet (UV) and blue light during the day. Previous work in the Holmes lab using fruit flies (which are related to mosquitoes) has determined the light sensors and circadian molecular mechanisms for light mediated attraction/avoidance behaviors. Accordingly, molecular disruption of the circadian clock severely interferes with light-evoked attraction and avoidance behaviors in mosquitoes. At present, light-based insect controls do not take into consideration the day versus night behavioral profiles that change with daily light and dark cycles.

Light is the primary regulator of circadian rhythms and evokes a wide range of time-of-day specific behaviors, said Holmes. By gaining an understanding of how insects respond to short wavelength light in a species-specific manner, we can develop new, environmentally friendly alternatives to controlling harmful insects more effectively and reduce the need for environmentally damaging toxic pesticides.

This study was funded in part by the National Institutes of Health, National Science Foundation and the ARCS Foundation. This new research builds on the Holmes labs previous studies at the UCI School of Medicine published over the past few years in Science, Nature and Proceedings of the National Academy of Sciences.

About the UCI School of Medicine

Each year, the UCI School of Medicine educates more than 400 medical students, and nearly 150 doctoral and masters students. More than 700 residents and fellows are trained at UCI Medical Center and affiliated institutions. The School of Medicine offers an MD; a dual MD/PhD medical scientist training program; and PhDs and masters degrees in anatomy and neurobiology, biomedical sciences, genetic counseling, epidemiology, environmental health sciences, pathology, pharmacology, physiology and biophysics, and translational sciences. Medical students also may pursue an MD/MBA, an MD/masters in public health, or an MD/masters degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Leadership Education to Advance Diversity-African, Black and Caribbean (LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit som.uci.edu.

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New study reveals how day- and night-biting mosquitoes respond differently to colors of light and time of day - Newswise

SOUTH SAN FRANCISCO, Calif., July 22, 2020 /PRNewswire/ --Encoded Therapeutics, Inc.(Encoded), a precision gene therapy company, today announced it has raised $135 million in an oversubscribed Series D financing. The company also announced that its lead asset, ETX101, was granted Orphan Drug Designation (ODD) and Rare Pediatric Disease Designation by the U.S. Food and Drug Administration (FDA) for the treatment of SCN1A+ Dravet Syndrome.

GV (formerly Google Ventures) led the Series D financing with participation from Matrix Capital Management, ARCH Venture Partners, Illumina Ventures, RTW Investments, Boxer Capital, Nolan Capital, HBM Genomics, Menlo Ventures, Meritech Capital, Farallon Capital Management, SoftBank Vision Fund 21, and additional unnamed investors.

"I am incredibly proud of the progress our organization has made over the past year. We have built an outstanding team, further advanced ETX101 towards the clinic, applied our technology to a series of pipeline programs, and expanded our capabilities to become a fully integrated organization. We are grateful to our investors for supporting our vision to transform patients' lives with cell type-selective genetic medicines," said Encoded co-founder and chief executive officer, Kartik Ramamoorthi, Ph.D.

"Since 2019, our company has attracted some of gene therapy's most experienced executive leaders to prepare ETX101 for the clinic and beyond. This well-rounded team has made significant advances in manufacturing, clinical development, and regulatory affairs for ETX101. By coupling these with an innovative discovery engine, Encoded is advancing its preclinical pipeline of gene therapies to patients suffering from devastating pediatric CNS diseases," said Encoded's board chairman, Sean Nolan.

Encoded's discovery engine combines biological and computational approaches to identify and screen human DNA sequences known as regulatory elements at a high throughput scale. The resulting multi-dimensional, large scale datasets are leveraged to design optimal gene therapy expression cassettes which more precisely control transgene expression. By recapitulating natural patterns of gene expression, the resulting gene therapy vectors can provide maximal therapeutic benefit, minimize off-target expression, and address genetic disorders that have previously been considered untreatable.

David Schenkein, M.D., general partner and co-leader of GV's life sciences team, will join the Encoded Board of Directors as an observer. "Encoded's cutting edge platform has the potential to impact a broad range of diseases across different organ systems. Importantly, Encoded has translated this innovation into a one-time, first-in-class precision gene therapy candidate for the treatment of SCN1A+ Dravet Syndrome, a devastating pediatric disease with significant unmet medical need. I am enthusiastic to work with this top-tier team in their mission to treat these underserved patients and advance a portfolio of innovative medicines," said Dr. Schenkein.

The company also announced that ETX101 was granted Orphan Disease and Rare Pediatric Disease Designation by FDA. Both programs offer incentives for the development of therapeutics for underserved populations.

Proceeds from the Series D will be used to conduct clinical trial activities including a natural history study to better understand the progression of SCN1A+ Dravet Syndrome as well as first-in-human trials for ETX101. Additionally, the funds will support progression of the company's pipeline of gene therapies being evaluated for additional pediatric CNS disorders.

About EncodedEncoded Therapeutics, Inc., is a biotechnology company developing precision gene therapies for a broad range of severe genetic disorders. Seeded by Venrock, ARCH Venture Partners, Illumina Ventures, andMatrix Capital Mangament, ourmission is to realize the potential of genomics-driven precision medicine by overcoming key limitations of viral gene therapy. We focus on delivering life-changing advances that move away from disease management and towards lasting disease modification. We are advancing our lead asset, ETX101, for the treatment of SCN1A+ Dravet Syndrome. For more information, please visitwww.Encoded.com.

About Dravet SyndromeDravet syndrome is a rare, severe genetic disorder that occurs in approximately 1 in 16,000 births worldwide. The disorder is characterized by uncontrolled seizures, ataxia, significant developmental delays, and an increased risk of early mortality due to sudden unexpected death in epilepsy (SUDEP). The majority of Dravet Syndrome cases are caused by loss-of-function mutations in the SCN1A gene. Current treatments reduce seizures but do not address the underlying cause of the disorderSCN1A haploinsufficiency. More information about Dravet Syndrome can be found at http://www.dravetfoundation.org.

Media Contacts

Sarah SuttonGlover Park Group[emailprotected]202-337-0808

Danielle CanteyGlover Park Group[emailprotected] 202-337-0808

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As of the date of this press release, SoftBank Group Corp. has made capital contributions to allow investments by SoftBank Vision Fund 2 ("SVF 2") in certain portfolio companies. The information included herein is made for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy limited partnership interests in any fund, including SVF 2. SVF 2 has yet to have an external close, and any potential third-party investors shall receive additional information related to any SVF 2 investments prior to closing.

SOURCE Encoded Therapeutics, Inc.

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Encoded Therapeutics Announces $135 Million Series D Financing to Support First Clinical Trials in SCN1A+ Dravet Syndrome and Advance Preclinical...