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WISCONSIN RAPIDS They thought their newborn baby was perfect, but a Wisconsin couple soon discovered he had a deadly disease. The FOX6 Investigators found the state of Wisconsin has, so far, declined to test newborns for the rare condition that killed their son.

It's a genetic disorder known as Krabbe disease, which affects fewer than 1 in 100,000 children. Experts say early detection is critical to an affected child's chances of survival. Other states are adding newborn screening for Krabbe, but state officials in Wisconsin say there's not enough research to justify the four-dollar test.

The first day of parenthood is all about nerves, and relief.

"What do I do?!" Kevin Cushman recalls thinking, the day his son, Collin, was born. "'I don't know what to do!' I said, 'Is he OK?' And she said, 'He's perfect.'"

"And he was," said Judy Cushman, Collin's mom. "I mean, he was perfect when he was born. He was perfect."

Kevin always wanted a boy, but he and Judy agreed that's not what mattered most.

"Just as long as they're healthy," he said.

"As long as the child is healthy," Judy repeated. "And I had every reason to believe that my child was going to be healthy."

Ten years later, they can hardly remember thosefirst few months when Collin was just like any other baby.

What they will never forget is when everything changed.

"His whole body is stiff," Kevin says in a home video recorded when Collin was about 9 months old.

That's when Collin's muscles began to get tight. His reactions slowed. He became incessantly irritable. And, eventually, his face fell into an open-mouthed expression that would never go away.

"I remember holding Collin with tears, going, 'What's wrong with my son?'" Kevin said.

The answer was worse than they'd ever imagined. Collin had a rare, genetic disorder known as Krabbe disease. That meant he was going to die at an early age.

"You know, your dreams are shattered," Kevin said.

First, there would be years of tube feedings, vibration machines, and round-the-clock care.

"It was... challenging," Kevin said.

Collin was lucky enough to survive until the age of 9. Most Krabbe children die before they turn 2.

"It's horrifying," said Dr. Barbara Burton, a specialist in genetic medicine at Lurie Children's Hospital of Chicago.

She says Krabbe disease is a form of leukodystrophy that causes the body's nerves to degenerate.

"You lose the coating on the nerve fibers that transmit signals from one nerve cell to another," said Dr. Burton.

"So as the myelin was destroyed, [Collin] slowly lost more and more abilities," his father said.

The disease affects fewer than one in every 100,000 newborns -- perhaps even as few as one in 400,000 -- and there is no cure. There is, however, a way to treat the disease and improve a child's chance of living a longer, more functional life.

"We would've had a totally different boy," Judy said.

The trouble is, the treatment -- a hematopoietic stem cell transplant, or HSCT -- only works to treat Krabbe if it's done within a baby's first 30 days alive. Most parents have no idea their child even has the disease until symptoms surface months later.

"By the time the symptoms show themselves, it's too late," Kevin said. "There's no hope."

In 2018, Dr. Burton joined a team of experts in publishing guidelines that recommend newborns be screened for Krabbe before they leave the hospital. All 50 states already have programs to test newborns for a host of other disorders by pricking the child's heel to draw blood and placing that blood inside circles on a laboratory test card.

"It might just be another circle that they fill out," Kevin Cushman said.

New York was the first state to start testing for Krabbe in 2006, followed by Missouri, Kentucky, Ohio, Tennessee, and Illinois. At least five more states are now working to implement the screening, but so far, Wisconsin has rejected efforts to add Krabbe to the 48 disorders tested for at birth, in part, because there's not enough long-term research to prove the treatment works.

"I hear that argument over and over again, and I think it's ridiculous because the same thing could be said for almost any other condition for which we do newborn screening," said Dr. Burton.

Five years ago, the Cushmans nominated Krabbe disease for inclusion in Wisconsin's newborn screening program, but Chuck Warzecha, deputy administrator for the Wisconsin Division of Public Health, said the test results in too many "false positives."

"There are some risks and emotional impacts on the family when they get that false positive," said Warzecha.

The state's 2015 review of Krabbe testing relied on research that's now more than 10 years old and Dr. Burton says newer testing is more accurate.

"Our technology has gotten much better," said Dr. Burton.

In addition, some Krabbe patients who have gotten transplants are living longer more functional lives.

"We know if it gets detected early that it's treatable," said Senator Patrick Testin, a Stevens Point Republican. He's working on a bill to require Krabbe testing in Wisconsin -- as long as the cost doesn't derail his plan.

"Yeah, that might be a potential roadblock," Testin said.

In 2015, the state said Krabbe screening would cost an extra $300,000 a year, or roughly $4 per test.

"For $4, why wouldn't you?" Judy asked.

"Try to imagine yourself in the shoes of a family who finds out their child has Krabbe disease, and then talk about whether $4 per baby is worth it," Dr. Burton said.

"No child should have to go through this," Kevin said.

Even if Collin had been tested for Krabbe at birth, the Cushmans can't say for sure if they would have gone through with a transplant. The procedure is risky, and some children don't survive.

"I would've given anything to have had that choice," Kevin said. "Even if it didn't change the outcome. As a father, I think I would've felt at least a little more comfortable knowing that I literally did everything I could to save my child."

Of course, the risk of an early death without the transplant is 100%.

On Jan. 6, 2019 -- seven years to the day after Collin was diagnosed -- his father held him for the last time.

"I was gonna hold him as long as it took," he said. "If it took two days before he passed, I was not gonna let go of him."

It's not how the Cushmans imagined things when they welcomed their firstborn child into the world, but they couldn't have asked for a better goodbye.

"Surrounded by family," said Kevin Cushman. "It was perfect."

Krabbe is not on the federal government's recommended list of disorders for newborn screening, but two similar disorders are, including Pompe disease. The state of Wisconsin recently completed a pilot project for Pompe, and they are considering whether to test for it permanently. If they do, DHS says adding Krabbe testing after that would be less expensive than it would have been in the past, because the equipment and training would be similar.

For now, Krabbe is not part of Wisconsin's newborn screening program. The Cushmans intend to keep pushing until it is.

Krabbe is a recessive genetic disorder that is passed down, like blue eyes or attached earlobes. A child is only at risk if both parents are carriers of the mutated gene that causes Krabbe. Even then, there's only a 25% chance the child will get the Krabbe gene from both of them.

Parents can be tested before having a baby to determine if they are carriers of the disease, but -- because it is so rare -- most soon-to-be parents know nothing about it.

Even after Collin was diagnosed, the Cushmans chose to have a second child. This time, they knew there was a 25% risk the second child would have Krabbe. Judy Cushman called it "the worst lottery ever."

Fortunately for them, Kendra Cushman was born without the disease. Five years later, she is symptom free.

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Whats wrong with my son? Wisconsin rejects $4 test for rare, terminal disease - WITI FOX 6 Milwaukee

VANCOUVER, Washington, Jan. 21, 2020 (GLOBE NEWSWIRE) -- CytoDyn Inc. (CYDY), (CytoDyn or the Company"), a late-stage biotechnology company developing leronlimab (PRO 140), a CCR5 antagonist with the potential for multiple therapeutic indications, announced today that Alan P. Timmins, former President, Chief Operating Officer, and Board Member of Sarepta Therapeutics, Inc., a Nasdaq-listed company,has joined its board of directors as an independent director and chair of the boards Audit Committee.

Timmins brings a wealth of financial and operations experience to CytoDyns board. He previously served 16 years in various positions including President, Executive Vice President, Chief Operating Officer and Chief Financial Officer of Sarepta Therapeutics, Inc., a publicly traded life sciences technology company focused on precision genetic medicine. His leadership and drive contributed to a period of significant growth and he led several of the companys strategic, financing, M&A and out-licensing activities. He is currently the Vice President for Financial Affairs at the University of Portland, a position he has served in for over 8 years, focusing on all financial functions and on strategic planning and implementation across the organization. Earlier in his career, Timmins was a Senior Manager at PriceWaterhouseCoopers in the audit practice.

Timmins has also served as a member of boards of directors and as a volunteer for several public, private and not-for-profit companies, providing support in the areas of finance, business development, strategy, operations management and career planning, as well as doing guest lectures and seminars for area graduate and undergraduate students.

Over the course of his career, Alan has led major growth initiatives he was a key member of the team that built Sarepta Therapeutics into the company is it today, negotiating major commercial and governmental contracts, raising approximately $250 million, completing a strategic acquisition, and finalizing two out-licensing transactions,said Scott Kelly, M.D., CytoDyns Chairman of the Board. Alan has accumulated an impressive array of strategic, financial and commercial achievements and has demonstrated his ability to be a successful and trusted leader. His breadth of experience will be instrumental to the Audit Committee and to CytoDyn as a whole.

I am pleased to be joining the CytoDyn board of directors at this important time in the Companys development, said Timmins. Helping the Company reach its considerable potential in the important therapeutic areas of HIV, cancer and immunology will be a worthy and challenging goal, and I look forward to assisting management and the board in reaching that goal.

Scott Kelly, M.D. added, I would like to extend my sincerest gratitude to Michael Klump for serving on the board of directors of CytoDyn. Michael provided us with invaluable guidance and vision at a critical time for our company. Michael remains an ardent supporter of the science of CytoDyn and a significant investor. While Michaels increasing business responsibilities drove his decision to step down from our board, I am thrilled that he will remain an advisor to both the CEO and Chairman of the Board.

About Leronlimab (PRO 140)Leronlimab (PRO 140) is a humanized IgG4 monoclonal antibody that blocks CCR5, a cellular receptor that plays multiple roles with implications in HIV infection, tumor metastasis, and immune signaling.

In the setting of HIV/AIDS, leronlimab belongs to a new class of therapeutics called viral-entry inhibitors; it masks CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. At the same time, leronlimab does not appear to interfere with the normal function of CCR5 in mediating immune responses. Leronlimab has been the subject of seven clinical trials, each demonstrating efficacy by significantly reducing or controlling HIV viral load in human test subjects. Leronlimab has been designated a fast track product by the FDA. The leronlimab antibody appears to be a powerful antiviral agent leading to potentially fewer side effects and less frequent dosing requirements compared with daily drug therapies currently in use.

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In the setting of cancer, research has shown that CCR5 plays a central role in tumor invasion and metastasis and that increased CCR5 expression is an indicator of disease status in breast cancer. Moreover, researchers have shown that drugs that block CCR5 can block tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. CytoDyn is conducting additional research with leronlimab in the cancer setting and has initiated a Phase 1b/2 human clinical trial, as recently approved in 2018 by the FDA.

The CCR5 receptor also plays a central role in modulating immune cell trafficking to sites of inflammation and it is crucial for the development of acute graft-versus-host disease (GvHD) and other inflammatory conditions. Clinical studies by others have shown that blocking CCR5 using a chemical inhibitor can reduce the clinical impact of acute GvHD without significantly affecting the engraftment of transplanted bone marrow stem cells. CytoDyn is currently conducting a Phase 2 clinical study with leronlimab to further support the concept that the CCR5 receptor on engrafted cells is critical for the development of acute GvHD and that blocking this receptor from recognizing certain immune signaling molecules is a viable approach to mitigating acute GvHD. The FDA has granted orphan drug designation to leronlimab for the prevention of GvHD.

About CytoDynCytoDyn is a biotechnology company developing innovative treatments for multiple therapeutic indications based on leronlimab, a novel humanized monoclonal antibody targeting the CCR5 receptor. CCR5 appears to play a key role in the ability of HIV to enter and infect healthy T-cells. The CCR5 receptor also appears to be implicated in tumor metastasis and in immune-mediated illnesses, such as GvHD and NASH. CytoDyn has successfully completed a Phase 3 pivotal trial with leronlimab in combination with standard anti-retroviral therapies in HIV-infected treatment-experienced patients. CytoDyn plans to seek FDA approval for leronlimab in combination therapy and plans to complete the filing of a Biologics License Application (BLA) in the first quarter of 2020 for that indication. CytoDyn is also conducting a Phase 3 investigative trial with leronlimab (PRO 140) as a once-weekly monotherapy for HIV-infected patients and, plans to initiate a registration-directed study of leronlimab monotherapy indication, which if successful, could support a label extension. Clinical results to date from multiple trials have shown that leronlimab (PRO 140) can significantly reduce viral burden in people infected with HIV with no reported drug-related serious adverse events (SAEs). Moreover, results from a Phase 2b/3 clinical trial demonstrated that leronlimab monotherapy can prevent viral escape in HIV-infected patients, with some patients on leronlimab monotherapy remaining virally suppressed for more than five years. CytoDyn is also conducting a Phase 2 trial to evaluate leronlimab for the prevention of GvHD and a Phase 1b/2 clinical trial with leronlimab in metastatic triple-negative breast cancer. More information is at http://www.cytodyn.com.

Forward-Looking StatementsThis press releasecontains certain forward-looking statements that involve risks, uncertainties and assumptions that are difficult to predict. Words and expressions reflecting optimism, satisfaction or disappointment with current prospects, as well as words such as believes, hopes, intends, estimates, expects, projects, plans, anticipates and variations thereof, or the use of future tense, identify forward-looking statements, but their absence does not mean that a statement is not forward-looking. The Companys forward-looking statements are not guarantees of performance, and actual results could vary materially from those contained in or expressed by such statements due to risks and uncertainties including: (i)the sufficiency of the Companys cash position, (ii)the Companys ability to raise additional capital to fund its operations, (iii) the Companys ability to meet its debt obligations, if any, (iv)the Companys ability to enter into partnership or licensing arrangements with third parties, (v)the Companys ability to identify patients to enroll in its clinical trials in a timely fashion, (vi)the Companys ability to achieve approval of a marketable product, (vii)the design, implementation and conduct of the Companys clinical trials, (viii)the results of the Companys clinical trials, including the possibility of unfavorable clinical trial results, (ix)the market for, and marketability of, any product that is approved, (x)the existence or development of vaccines, drugs, or other treatments that are viewed by medical professionals or patients as superior to the Companys products, (xi)regulatory initiatives, compliance with governmental regulations and the regulatory approval process, (xii)general economic and business conditions, (xiii)changes in foreign, political, and social conditions, and (xiv)various other matters, many of which are beyond the Companys control. The Company urges investors to consider specifically the various risk factors identified in its most recent Form10-K, and any risk factors or cautionary statements included in any subsequent Form10-Q or Form8-K, filed with the Securities and Exchange Commission. Except as required by law, the Company does not undertake any responsibility to update any forward-looking statements to take into account events or circumstances that occur after the date of this press release.

CONTACTSMedia:Grace FotiadesLifeSci Communicationsgfotiades@lifescicomms.com(646) 876-502

Investors: Nader Pourhassan, Ph.D.President & CEOnpourhassan@cytodyn.com

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CytoDyn Appoints Alan Timmins as New Independent Director and Chair of the Audit Committee - Yahoo Finance

SALT LAKE CITY, Jan. 22, 2020 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, announced that it has submitted a supplementary premarket approval (sPMA) application to the U.S. Food and Drug Administration (FDA) for its myChoice CDx test to help predict outcomes of women with first-line platinum responsive advanced ovarian cancer treated with GSKs PARP inhibitor Zejula (niraparib). Myriads filing is based on the positive results from the Phase 3 PRIMA trial of Zejula that was published online in the New England Journal of Medicine in September 2019.

The myChoice CDx test provides valuable molecular insights into tumors and helps identify women with ovarian cancer who are most likely to benefit from PARP inhibitors, said Nicole Lambert, president, Myriad Oncology. This regulatory submission represents another important step forward for precision medicine and ensuring that women have access to the most advanced therapies.

Myriad's myChoice CDx is the most comprehensive homologous recombination deficiency test, enabling physicians to identify patients with tumors that have lost the ability to repair double-stranded DNA breaks, resulting in increased susceptibility to DNA-damaging drugs such as platinum drugs or PARP inhibitors. The myChoice CDx test comprises tumor sequencing of the BRCA1 and BRCA2 genes and a composite of three proprietary technologies (loss of heterozygosity, telomeric allelic imbalance and large-scale state transitions).

About Ovarian CancerOvarian cancer affects approximately 22,000 women per year in the United States according to the American Cancer Society. Typically, ovarian cancer is diagnosed at later stages when it has metastasised to other areas of the body and only 20 percent of patients are diagnosed with early stage disease. Ovarian cancer is one of the deadliest cancers with approximately 14,000 deaths per year attributed to the disease. Patients with certain characteristics such as a family history of the disease, certain genetic mutations such as those in the BRCA1 and BRCA2 genes, obesity and endometriosis face a higher risk from ovarian cancer.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision 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 five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. 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, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel 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.

GSK is commercializing ZEJULA. ZEJULA is a registered trademark of GSK.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to women getting access to the most advanced therapies; and the Company's 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: 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 decision in the lawsuit brought against us by the Association for Molecular Pathology et al; 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.

Originally posted here:
Myriad Submits sPMA for myChoice CDx with Zejula in First-Line Platinum Responsive Advanced Ovarian Cancer - GlobeNewswire

Brain food: Autism appears to be closely linked to headaches.

Maya23K / iStock

People with autism have more brain-related health problems, such as headaches and epilepsy, than typical people do, according to a survey of twins1. The study is the first to look at associations between autism and physical health problems among twins.

The study found no association between autism and other physical conditions, such as gastrointestinal problems and infectious diseases, however.

I find it particularly remarkable that our results are so clear in terms of confirming that [autism] but also autistic traits are associated with neurological alterations, and no other somatic issues are equally associated, says lead investigator Sven Blte, director of the Center of Neurodevelopmental Disorders at the Karolinska Institutet in Stockholm, Sweden. The findings also support the idea that autism is a condition of the brain, Blte says, and not of the immune system or the gut.

Understanding associations such as these can help clinicians look out for autistic peoples health problems. That is particularly important when treating people who may have difficulties communicating, says Thomas Challman, medical director of the Geisinger Autism and Developmental Medicine Institute in Lewisburg, Pennsylvania.

Associated health issues can be really important in maximizing peoples quality of life, Challman says. If there is a higher rate of various other medical conditions in individuals with a developmental condition, we want to have a higher level of alertness in detecting these things.

The researchers surveyed 172 pairs of twins both identical and fraternal enrolled in the Roots of Autism and ADHD Twin Study Sweden. Of this group, 75 pairs have at least one twin with autism; 18 pairs of identical twins have only one twin with autism. Because identical twins who grow up together share a nearly identical genetic background and environment, they are particularly helpful in teasing out how these factors can shape an individuals health.

The researchers gave the participants, who ranged in age from 8 to 31 years, diagnostic exams and the Social Responsiveness Scale, Second Edition, a standard survey of autism traits. The participants or their parents then filled out a questionnaire that asked about the participants history of infectious and cardiovascular diseases, neurological problems such as epilepsy and headaches, gastrointestinal problems such as lactose intolerance, and immunological conditions such as asthma and allergies.

The researchers found that people with an autism diagnosis have more neurological and immunological health problems than those without the diagnosis. They also found that within identical twin pairs in which only one twin has autism, the twin with more neurological problems is more likely to be autistic than the neurotypical twin is.

In their analysis, the researchers weighted common problems such as headaches as equal to rarer problems such as heart defects. This approach may have affected the results, so the team should confirm the finding in a larger sample size, says Lior Brimberg, who was not involved in the research. Brimberg is assistant professor of neuroimmunology at the Feinstein Institute for Medical Research in Manhasset, New York.

The researchers also did not control for age or gender.

The fact that the study did not find an association between autism and gastrointestinal problems is surprising, notes Barbara McElhanon, assistant professor of pediatric gastroenterology at Emory University in Atlanta, Georgia, and a clinician at Childrens Healthcare of Atlanta.

The study may have missed this association because gastrointestinal problems, such as constipation, tend to be transient, she says, and may be more easily forgotten when responding to questionnaires than are persistent conditions such as epilepsy. Only 1.2 percent of the participants with autism and 0.8 percent of those without autism reported experiencing constipation both at the low end of prevalence estimates in the general public, which range from 0.7 to nearly 30 percent.

The study is also important in evaluating how much of autism and its traits are heritable versus environmental, Brimberg says.

Because identical twins share nearly all of their DNA, the association between autism and neurological problems in identical twins suggests that something beyond genetics, such as an interaction between genes and the environment, is at play in the origin of both conditions, Brimberg says.

Theyre almost sharing the same environment, theyre almost sharing the same genetics, and you still dont see 100 percent penetration of [autism], Brimberg says.

Brimberg notes that a study in July concluded that autism is 80 percent heritable2. I think this study suggests that, you know, not necessarily, she says.

The researchers hope to analyze a larger database, such as the Child and Adolescent Twin Study in Sweden, which has more than 32,000 participants. Ultimately, they say, they hope their work will help scientists identify autism subtypes and pathways that underlie the condition.

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Autistic people have increased incidence of neurological problems - Spectrum

KING OF PRUSSIA, Pa., Jan. 22, 2020 /PRNewswire/--The Discovery Labs and Deerfield Management Company have formed The Center for Breakthrough Medicines, a Contract Development and Manufacturing Organization (CDMO) and specialty investment company, to alleviate the critical lack of capacity that is preventing patients from accessing critically needed cell and gene therapies. The CDMO is occupying over 40 percent of The Discovery Labs' 1.6 million square foot biotech, healthcare and life sciences campus in King of Prussia, PA.

The CDMO provides preclinical through commercial manufacturing of cell and gene therapies and component raw materials. It offers process development, plasmid DNA,viral vectors, cell banking, cell processing, and support testing capabilities all under one roof. The immense $1.1 billion facility will provide instant capacity as the largest known single source for accelerating the delivery and affordability of lifesaving and life-changing therapies from the bench to the patient's bedside.

The Company has initiated a substantial hiring effort targeting the best and brightest of the life sciences community including, experts in CGMP manufacturing. The Company expects to hire over 2,000 team members within the next 30 months.

The CDMO has retained Nucleus Careers, a cloud-based specialty life sciences human capital recruiting and retention management expert, to buildout the entire team. Nucleus has proprietary recruiting and retention software designed for large scale human capital buildouts of high growth companies.

In addition to developing the world's largest single-point cell and gene therapy manufacturing facility, The Discovery Labs is establishing THE COLONY which will provide custom built discovery labs, breakthrough funding, sponsored research agreements, housing and relocation for the world's leading iconic experts in cell and gene therapy.

THE COLONY will seek to work hand in hand with scientists from both academic and pharmaceutical institutions to unlock and expedite groundbreaking therapies.

Marco A. Chacn, Ph.D., Founder of Paragon Bioservices and Chairman of The Discovery Labs states, "musicians, artists, members of religious communities and great thinkers throughout time have formed colonies where freedom of thought and expression combined with unlimited dreams and potential have resulted in the world's greatest accomplishments." Dr. Chacn went on to say, "the goal of THE COLONY is to unshackle the potential of the world's greatest scientific minds."

The ability for the industry's greatest scientists to cohabitate, collaborate, cooperate, and communicate via technology and in person will create an exponential therapeutic "X FACTOR." THE COLONY seeks to unlock institutional barriers prohibiting the world's greatest scientists from moving at a pace necessary in today's ever-changing therapeutic revolution. THE COLONY will partner with the institutions where the scientists currently work by providing equity, license fees, and revenue sharing.

"The Center for Breakthrough Medicines will be serving companies from the earliest stages through commercialization. Its exceptional scale and offering will quickly relieve the production bottleneck for advanced therapies by reducing the time, complexity, and cost of commercializing vitally needed gene and cell therapies," noted Audrey Greenberg, Board Member and Executive Managing Director for The Discovery Labs.

The addition of this end-to-end manufacturing capability is expected to significantly enhance the offerings of The Discovery Labs in an area that has become one of the largest life sciences hubs in the world. Renovations are underway to construct a total of 86 plasmid, viral vector production, universal cell processing, CGMP testing, process development and cell banking suites. The viral vector and cell processing suites will be fully compliant with both U.S. Food and Drug Administration and European Medicines Agency standards. All suites will offer the flexibility to meet client-specific workflows and will be able to adapt quickly to meet demand. The Company is in the process of reserving capacity now for late 2020.

"Today brilliant scientists are advancing an unprecedented number of gene and cell therapy drug candidates. The real tragedy, however, is a scarcity of manufacturing know-how, which is complex and expensive," said Alex Karnal, Partner and Managing Director of Deerfield Management and a Board Member of the Discovery Labs. "With its visionary business model, it is hoped that The Center for Breakthrough Medicines will help realize the promise of cell and gene therapies in time to treat the many patients who need them."

The Discovery Labs provides a central campus where the world's greatest scientists can collaborate on new therapeutic discoveries to eradicate diseases affecting small and large segments of the global population. The Center for Breakthrough Medicines will work with these leaders, life sciences companies, large pharmaceutical companies, and academic and government institutions.

This new manufacturing capability is a transformational addition to The Discovery Labs market offering and dovetails with The Discovery Labs biotech incubator, Unite IQ. Unite IQ offers immediate space to emerging life sciences companies and scientists giving them the ability to grow from startup to enterprise company on one campus. The incubator and accelerator space at Unite IQ provides a comprehensive home for startups with every resource needed to initiate business operations. Unite IQ tenants are expected to utilize the discovery, development, testing, and manufacturing capabilities of the Center for Breakthrough Medicines with seamless forward integration of processes and analytics, and seamless tech transfer from research lab to large scale production

The Emerging Field of Cell and Gene Therapy in Pennsylvania

The demand for clinical and commercial manufacturing capacity is acute and expected to remain that way. The current shortfall in manufacturing for cell and gene therapies is severely underserved with few approved products. There are currently approximately 1,100 advanced therapies in the pipeline pending FDA approval. This will greatly increase highly skilled manufacturing demand. Dr. Peter Marks, Director of the FDA Center for Biologics Evaluation and Research, states, "what keeps me up at night is will we be able to manufacture these on a scale that will allow us to bring the benefit of these therapies to patients?"He further added that "if we can help see cost of goods and ability to manufacture reproducibly improve, I think that'll be a big thing."All of this adds up to a supply constrained market that The Center for Breakthrough Medicines aims to help address.

With the potential to treat and even cure disabling, and deadly diseases, gene and cell therapies are ushering in a new era of medicine. These therapies may eventually be able to cure genetic conditions, such as cystic fibrosis, hemophilia A, and a range of cancers. The Philadelphia area has become the epicenter for the flourishing field of gene and cell therapy. Research from CBRE currently ranks the market among the top biotech clusters for medical research and health services. The cluster has become known worldwide as "Cellicon Valley"for its leadership in research and development of this rapidly evolving field. The Discovery Lab's suburban Philadelphia location offers a talent rich environment due to the area's preponderance of large pharmaceutical companies and the Philadelphia region's position boasting the top 10 universities and primary school systems in nation.

Over the past three years, multiple Philadelphia companies have received approvals for major breakthroughs in cell and gene therapy. In 2017, the U.S. FDA approved the first-ever CAR-T cell therapy, Novartis's Kymriah, which originated at the University of Pennsylvania. Shortly thereafter, the FDA gave landmark approval for the first-ever gene therapy to treat a genetic blindness condition to Spark Therapeutics, a start-up founded by researchers at Children's Hospital of Philadelphia. These discoveries and others in the pipeline are attracting billions of dollars of venture capital. The Greater Philadelphia Region set a recent record in venture capital financing.

The Discovery Labs Center for Breakthrough Medicines joins more than 25 healthcare, life sciences and tech-enabled companies that already call The Discovery Labs King of Prussia home.

Brian O'Neill, Founder of The Discovery Labs Center for Breakthrough Medicines, and Tony Khoury, Board Member of The Discovery Labs and Engineer at Project Pharma, will be speaking at the 2020 PhacilitateWorld Stem Cell Summit discussing The Future of Gene Therapy Manufacturing at 4 p.m. today at the Hyatt Regency in Miami, Florida.

Contact Audrey Greenberg at agreenberg@thediscoverylabs.com for more information about development services, manufacturing capacity, incubator space or leasing information at the property.

About The Discovery LabsPart of MLP Ventures, The Discovery Labs is a global provider of world-class cGMP manufacturing, turnkey laboratory solutions, critical materials and office space that support therapeutic products and services to the biotechnology and pharmaceutical industry so that groundbreaking medicines get to the patients that need them. The location in eastern King of Prussia is a prototype for a global rollout of The Discovery Labs, providing Big Pharma, emerging life sciences, consumer and technology companies flexible, end-to-end technical real estate and business infrastructure for the customer's entire lifecycle from discovery to delivery, including manufacturing capacity. It is the first fully integrated environment that merges technology and life sciences under one roof to drive innovation.

About Deerfield Management

Deerfield is a healthcare investment management firm committed to advancing healthcare through investment, information and philanthropy.

Media Contact:Tony DeFazio, DeFazio Communications(o) 484-534-3306 (c) 484-410-1354tony@defaziocommunications.com

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The Center for Breakthrough Medicines is Building the World's Largest Cell and Gene Therapy Contract Development and Manufacturing Organization (CDMO)...

22nd January 2020

Categories: Latest News

A new method undergoing trial in Manchester could save newborns from permanent deafness with a simple cheek swap, sparing more than 180 babies profound hearing loss a year and could save the NHS millions, reports award-winning health writer and Guardian contributor, Rachel Pugh.

The swab means that nurses can identify whether a premature baby would be genetically predisposed to being left deaf after treatment with gentamicin, a life-saving antibiotic used to treat 90,000 newborns a year. Guidelines say a baby should have gentamicin administered within an hour, though researchers have known for 25 years that the antibiotic could lead to deafness caused by a genetic variant which affects 1 in 500 people. Testing for it has traditionally taken days.

But now, in just 20 minutes a nurse working alone can establish, by placing cells from a babys cheek swab into a into a PC-sized molecular-diagnostic bedside machine, whether their infant patient has the genetic variant which rules out using gentamicin and if so to prescribe an alternative drug instead.

The test, which already has Health Research Authority, CE and ethical approval, has just started trials in neonatal intensive care units at St Marys Childrens Hospital Manchester and Liverpool Womens Hospital. Used across the NHS, it could save more than 180 babies a year from going deaf as a result of gentamicin.

Bill Newman, professor of Translational Genomic Medicine at the University of Manchester who is leading the trial, says that the technology could be used in future to identify how patients are affected by other drugs. Mr Newman whose team includes the developers of the testing equipment genedrive plc and parents of children treated in NICUs said:

Successful implementation of the gentamicin test will be a first in the integration of a rapid decision-making, genetic-based diagnostic in the UK NHS. It opens the door to getting much better outcomes for a number of other diseases too now that the test is out there.

In addition to saving families from the emotional anguish of a diagnosis of profound deafness, the success of the Pharmacogenetics to Avoid Loss of Hearing (PALoH) study will save the NHS an estimated 5m every year (including the cost of the test) in cochlear implantations and other hospital costs, according to health economists making up part of the team.

The Genedrive test costs around 60 per baby at the moment and was developed by the Manchester-based medical equipment company genedrive plc, in collaboration with Mr Newmans team. The development research took place at Manchester Biomedical Research Centre with 900,000 in funding from the National Institute for Health Research (NIHR) and support from the charity Action on Hearing Loss.

Mr Newman is convinced that the successful implementation of this trial will open the door to early detection of more common conditions. His team is already working with genedrive plc on a similar rapid bedside test for stroke patients to detect the one in 10 patients whose DNA makes them unable to metabolise clopidogrel, the common anti-platelet medication, and therefore have significantly worse outcomes. Models suggest similar tests could prevent several thousand of the 100,000 strokes suffered by people each year in the UK. It also opens up the possibility of using pharmacogenetics testing more widely by using biomarkers to target treatments more appropriately.

Mr Newman said:

It raises the long term possibility of developing a series of tests which might be given to everyone at the age of maybe 40 or 50 (when people start to develop health problems) to look at various genes that we know to be linked to specific drug outcomes. Health passports linked to electronic patient records might then be developed that contain information such as codeine does not work for this patient.

If the PALoH trial is successful, it could be rolled out across the NHS within a year, under National Institute for Health and Care Excellence (Nice) guidance. There is also interest in the bedside test from Australia, the USA, Israel and the Netherlands.

Health secretary Matt Hancock recently revealed ambitious plans for the NHS to introduce a form of DNA testing called whole exome sequencing for a range of inherited conditions at birth, to reduce their impact. It has currently been tried on 80 babies, and can provide a diagnosis in days rather than weeks.

Source: The Independent

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Manchester leading the way in the world's first emergency genetic test - Invest in Manchester

Led by T. Rowe Funds and Viking Global Investors, the funding allowed Color to accrue a number of new partners, which now comprise Apple, Verily, Northshore University HealthSystem,the Teamsters Health and Welfare Fund of Philadelphia and Vicinity, and Sanford Health.

Color has also announced that it is now working alongside not-for-profit healthcare system Sanford Health to build on its Imagenetics genomics programme, which will, in turn, allow Sanford Health to embed genetic medicine directly into primary care, as well as to implement Colors digital tools to engage patients and streamline clinical reporting within its facilities.

Caroline Savello, Vice-President of Commercial for Color,commented: "In the last 18 months, we saw a huge acceleration with institutions around the world and across every type of player in the health ecosystem whether its hospitals or health systems, large-scale research programmes, payers, care delivery or employers who want to change the care delivery model for their population by understanding genetics across the population.

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Color raises further $75-million funding - ITIJ

SAN FRANCISCO, Jan. 23, 2020 /PRNewswire-PRWeb/ -- ixLayer, a San Francisco based start-up is launching a first of its kind platform to simplify the complex relationship between precision health tests, physicians, and patients. The platform is the culmination of two years spent working closely with health systems, clinical laboratories, physicians, and patients. The venture backed company is funded by Health-tech focused firms such as Pear VC, FundRx, Village Global, and Maky Zanganeh & Associates.

"There has been a heavy focus on enabling direct to consumer genomics over the last couple of years, but we cannot forget that most of this testing is still being ordered in a clinic. We are now taking our expertise creating patient centric products within genomics and digitizing processes associated with ordering this complex testing in clinics. We want to make sure that both physicians and patients are at the center of everything we build." says CEO of ixLayer Pouria Sanae.

True to its name, the value of the platform is to be the "layer" of technology that brings together the key components needed to simplify the ordering and delivery of complex test results. These components include direct integrations into laboratories, on-demand genetic counseling services, integrations into electronic health records, patient engagement tools, and digital representation of patient health data.

The goal of the platform is to remove barriers to the adoption of precision medicine and speed up the launch and delivery of new diagnostic tools.

Current use cases of the platform include:

1. Providing an easy way for community physicians to work in partnership with labs to enroll patients into research studies involving diagnostic testing. The platform removes the burden of enrollment, patient education, sample collection, etc. from the physicians plate and gives the laboratory a dashboard with insight into what is happening at each site. This flow can also be used for enrolling patients into clinical trials and maintaining patient engagement, all through their patient portal.

2. Enabling large scale population health projects to roll out quickly without putting the burden of building infrastructure on the institution. The platform can easily engage community members and accelerate research and disease prevention at scale. By integrating with the health system electronic health record, the platform enables results from tests ordered virtually to be available directly to physicians.

3. Simplifying the process by which patients with rare diseases are engaged and identified. Many therapies today are based on biomarker testing which is typically only available in a physician's office. The ixLayer platform can be integrated into any patient website and walk a patient through the entire testing process. The platform is integrated with comprehensive physician and counseling services, who can then help triage that patient into local care for treatment.

ixLayer is partnering with the Innovation Institute and Invenio Genetics to streamline the delivery of genetic testing and results to its members. The first hospital to roll out testing on the ixLayer platform is Avera Health. Through ixLayer, Avera will offer genetic testing to over one million members.

"The most exciting part of this program is that these tests can be ordered online by physicians and results returned through the electronic record. Results will be available to patients and physicians to guide clinical care" says Joe Randolph CEO of Innovation Institute. "We saw a lot of precision medicine programs being launched in the market and realized one that recognized the patient and physician relationship is the best way to ensure appropriate patient care."

Looking forward, ixLayer is laser focused on improving the delivery of diagnostic testing. Whether testing is being offered through population health programs, the patient's physician, a consumer test, or a research study, ixLayer strives to provide optimal user experiences and transparency, "We want the platform to be a catalyst for dramatic change in the industry, getting patients engaged, and improving outcomes," Says Sanae.

Potential partners who are interested in learning more about how ixLayer is digitizing the ordering and delivery of precision health testing can visit:ixlayer.com/precision-health-testing platform-announcement

About ixLayer: Ixlayer powers the delivery of precision health testing for physicians, health systems, health focused companies, and pharmaceutical partners. The end to end solution brings together all of the components needed to deliver complex testing and results to patients. We are committed to improving outcomes and removing barriers to the access of precision medicine. For more information on Innovation Institute, please visit: ixlayer.com

About Innovation Institute: The Institute supports medical device innovation through its Innovation Lab where medical device and healthcare innovation solutions are developed. We also raise medical innovation funding to take the most important medical and healthcare innovations to the healthcare marketplace. We encourage innovators to submit their invention ideas to our Innovation Lab for cultivation. Our healthcare innovation experts provide the healthcare innovation support needed for success. The Lab sets forth local and global healthcare challenges to serve as facilitators of world healthcare innovation or world medical innovation.For more information on Innovation Institute, please visit: ii4change.com

Ixlayer Media Kit

SOURCE ixLayer

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ixLayer launches first-of-its-kind precision health testing platform to improve delivery of diagnostic testing - Benzinga

Diagnosed with a genetic disease that slowly eats away vital organs, and brushed aside by health bureaucrats, a family in Nizhny Novgorod have fought to obtain a crucial but expensive drug a battle they are now winning.

As millions of children across Russia prepared to open their Christmas presents, 12-year-old Ivan Lobanov, a resident of a small hamlet near Nizhny Novgorod, turned the camera on and began to speak, his voice calm and lips stiff.

I have a serious disease, the Fabry disease. I inherited it, the pale, intelligent-looking boy is heard to say in the video. My mother is sick, my cousins are sick, [as are] my uncle and grandmother, the boy said, bending his fingers.

I know that the medicine is expensive and we will never buy it on our own. But everyone has the right to life. Without medicine, we will die, he added in despair.

Intended for Vladimir Putin and shared on social media, Ivans cry for help has become a turning point for him and his family, who spent three years fighting for a life-saving medication refused to them by their clinic. But for some of the family, it came all too late.

Like many people who test positive for deadly diseases, the seven blood relatives whom Ivan had asked to help learned of their diagnosis by accident.

A blood test and subsequent DNA sample taken from one of the seven back in 2016 showed initial symptoms of Fabry. Later that year, the deadly diagnosis was confirmed in all of them by leading Moscow and St. Petersburg hospitals, Natalia Fedina, Ivans 32-year-old mother, told RT Russian.

Once back at home, the woman had the diagnosis confirmed by the nearest clinic. She and her loved ones had every reason to sound the alarm.

Discovered in 1898 by a German dermatologist, Fabry slowly consumes the kidneys, heart, blood system and skin, often causing unbearable body pain. It was almost a century before the first specific treatment for Fabry disease was invented and approved but decades of clinical research didnt make the drugs any more affordable.

READ MORE: Unique surgery: Russian hospital performs first successful lungs and liver transplant

The annual cost of fabrazyme and replagal two Western-made medicines developed to stop the disease from progressing is around US$100,000 per patient. And this is where the life of Ivan and his immediate family hung in the balance.

Natalia recalls how she asked local authorities to cover expenses for the costly medicine under a healthcare scheme technically available to every Russian free of charge.

All of a sudden, the appeal was rejected by the local health ministry officials, who claimed the diagnosis was wrong because... the clinic didnt have a geneticist among their staff.

But Natalia believes the authorities simply denied the treatment for seven relatives because the total costs would be overwhelming, given that the drug needs to be injected twice a month and is prescribed for life.

The clinics management and their superiors tried to prove the patients were healthy. They would say: Theres no such disease, what have you come up with? Natalia shared.

Fabry starts taking a heavy toll in early childhood, and this is what Ivan must cope with every day. Vanya, he has his kidney damaged, his arms and legs suffer from severe pain, his mother says.

You know, he comes back from school and says: I cant take it anymore, Ill be in the wheelchair soon or die.

Once symptoms recede, the 12-year-old may live a fairly normal life, playing computer games and dreaming of seeing the world.

I want to travel abroad and go to the sea, maybe Egypt or Tunisia, Ivan wistfully told the RT crew and smiled, but then broke off and got serious: My arms and legs ache in the heat. You dont sit still when travelling abroad, you walk or go sightseeing but I cant do so, it doesnt work that way.

As health officials played bureaucratic ping-pong, Natalia, Ivan and the relatives managed to receive the medication through a charitable organization for half a year. But since the treatment must not be interrupted, their symptoms deteriorated.

Eventually, the mother had to quit her job, and her uncle sadly died. 51 isnt the right age to die, he wasnt going to die, Natalia said, standing near his grave. He went to the treatment on his own and came back in a casket.

But after his death and, probably, Ivans footage something began to change. Natalia was contacted by local health authorities who assured her that the medicine is on its way to the local clinic and the treatment is due to start soon. She was also promised that an inquiry will be launched into their case.

After his death, things started to move. The health ministry and hospitals, and everyone drew attention to us, the woman says of her uncle. He sacrificed his life to save us all.

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Without it we will die: Denied expensive medication for 3yrs, Russian family fights (and wins) against rare genetic disease - RT

As we move into the next decade, we asked the editorial board of Neurology Today to reflect back on 2019 to highlight those advanceshowever large, small, or transformationalthat moved neurology and the field forward in the clinic, at the bench, in the therapeutic pipeline, and in areas of policy and practice. Here below they offer their expert picks on the neurology news that mattered in 2019. Look for more in-depth discussion of these picks and reports in NeurologyToday.com.

JAMES C. GROTTA, MD, FAAN

Director of Stroke Research at the Clinical Institute for Research and Innovation

Memorial Hermann-Texas Medical Center

Houston, TX

The Pick: Johnston KC, Bruno A, Pauls Q, et al. Intensive vs standard treatment of hyperglycemia and functional outcome in patients with acute ischemic stroke. The SHINE randomized clinical trial. JAMA 2019;322(4):326-335.

The Findings: This trial randomized 1,151 acute ischemic stroke patients with blood glucose>110 mg/dL (or >150 mg/dL if not diabetic) at admission to receive either aggressive blood glucose-lowering using an insulin drip, which achieved a mean glucose level of 118 mg/dL or a conventional insulin sliding scale, which achieved a mean glucose level of 179 mg/dL. Intensive management compared with standard management did not improve functional outcome, and intensive treatment was associated with more symptomatic hypoglycemia.

Why It's Important: Many patients with acute stroke are hyperglycemic on admission and hyperglycemia has been associated with increased brain swelling and bleeding. But it is not known if aggressively lowering elevated blood glucose will result in a better outcome. This study conclusively shows that aggressive reduction of blood glucose in the acute setting is not beneficial.

The Pick: Connolly SJ, Crowther M, Eikelboom JW, et al, for the ANNEXA-4 Investigators. Full study report of andexanet alfa for bleeding associated with factor Xa Inhibitors. N Engl J Med 2019;380(14):1326-1335.

The Findings: Andexanet alfa is a recombinant inactive form of factor Xa developed for reversal of factor Xa inhibitors. A total of 352 patients with acute major bleeding due to a factor Xa inhibitor (64 percent had intracranial hemorrhage) were given a bolus of andexanet followed by a two-hour infusion. Andexanet resulted in 92 percent reduction of factor Xa levels, and excellent or good hemostasis was achieved in 82 percent.

Why It's Important: Factor Xa inhibitors are safer and at least as effective as warfarin, so they are commonly used, including for prevention of stroke in patients with atrial fibrillation. Major bleeding complications including intracranial hemorrhage may occur. Andexanet is the first specific factor Xa inhibitor reversal agent designed to stop such bleeding. The major drawback of andexanet is its cost. Andexanet will likely become more commonly used in selected patients with life-threatening factor Xa-associated acute major bleeding and will provide further support for the use of Xa inhibitors over warfarin.

The Picks: Pan Y, Elm JJ, Easton JD, et al. Outcomes associated with clopidogrel-aspirin use in minor stroke or transient ischemic attack: A pooled analysis of CHANCE and POINT trials. JAMA Neurol 2019; Epub 2019 Aug 19.

Wang Y, Chen W, Lin Y, et al. Ticagrelor plus aspirin versus clopidogrel plus aspirin for platelet reactivity in patients with minor stroke or transient ischemic attack. BMJ 2019;365:12211.

Classens DMF, Vos GJA, Bergmeijer TO, et al. A genotype-guided strategy for oral P2Y12 Inhibitors in primary PCI. N Engl J Med 2019;381:1621-1631.

The Findings: The Pan, et al study pooled data on 10,051 patients from two large studies (CHANCE and POINT), which both showed that in patients with high-risk transient ischemic attack (TIA) or minor stroke, dual antiplatelet therapy (DAT) with clopidogrel plus aspirin resulted in fewer recurrent ischemic events than monotherapy with either aspirin or clopidogrel alone. However, the two studies had differing duration of DAT, and this pooled analysis showed that the benefit occurred with the first 21 days of treatment. After that, the risks of bleeding exceeded the benefit.

In CHANCE, Wang, et al had also shown that many patients on DAT continue to have heightened platelet reactivity, in particular those carrying the CYP2C19 loss-of-function allele. Ticagrelor is pharmacologically similar to clopidogrel but its metabolism does not involve the CYP2C19 pathway. Now the same investigators show that substituting ticagrelor for clopidogrel resulted in much more complete suppression of platelet reactivity without increased bleeding risk compared to those just left on clopidogrel plus aspirin.

Supporting this concept, Classens, et al randomized stroke patients with percutaneous coronary intervention (PCI) to receive either ticagrelor or prasugrel versus clopidogrel. Patients in the clopidogrel group who had CYP2C19 loss-of-function alleles were switched to ticagrelor or prasugrel. The genotype-guided group was non-inferior with regard to recurrent ischemic events and had less bleeding.

Why It's Important: Patients with minor stroke and some TIA patients are at high risk of recurrent ischemic events, and based on the CHANCE and POINT studies should be treated with DAT. The Pan, et al pooled analysis conclusively shows that such DAT should be stopped and patients reverted to monotherapy after 21 days. However, even if on DAT, many patients continue to have high platelet reactivity because they harbor the loss-of-function CYP2C19 allele that prevents the conversion of clopidogrel to its active form. Because ticagrelor and prasugrel metabolism do not involve the CYP2C19 pathway, and they are under evaluation to replace clopidogrel, these studies suggest that high-risk patients continued on clopidogrel should be checked for CYP2C19 activity, and ticagrelor substituted if loss-of-function is identified.

ANN TILTON, MD, FAAN

Professor of Neurology and Pediatrics

Louisiana State University Health Sciences Center

New Orleans, LA

The Pick: Kim J, Hu C, Moufawad EA, et al. Patient-customized oligonucleotide therapy for a rare genetic disease. N Engl J Med 2019;381(17):1644-1652.

The Findings: In this N of 1 study, investigators designed, tested, and manufactured milasen, a splice-modulating antisense oligonucleotide (ASO) drug tailored to a particular patient with a rare genetic form of Batten disease. There were no serious adverse events, and treatment was associated with a reduction in seizures (evidenced by EEG and parental reporting). This ability and the development of the ASO drug nusinersen for the treatment of infants and children with spinal muscular atrophy opened up the ability to utilize similar technology in the child in this study who was deteriorating.

Why It's Important: This study provides a proof-of-concept demonstrating an N of 1 studya patient-specific treatmentthat has thus far been safe and has some efficacy. The authors rapidly utilized genomic medicine to further open the door for individualized treatment in the rare disease space.

Read the Neurology Today story, In the Pipeline-An Antisense Oligonucleotide Therapy Looks Promising for a Rare Form of Batten Disease (June 20, 2019).

ERIC M. MCDADE, DO

Associate Professor of Neurology

Washington University at St. Louis

School of Medicine

St. Louis, MO

The Pick: Preische O, Schultz SA, Apel A, et al, for the Dominantly Inherited Alzheimer Network. Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease. Nat Med 2019;25(2):277-283.

The Findings: In this study, researchers studying a group of participants with autosomal dominant Alzheimer's disease (AD), a highly predictable form of the disease, measured serum and CSF neurofilament light chain (NfL)a neurospecific marker that increases with neuronal damage, across the disease spectrum to determine if NfL could provide unique information on disease stage and risk. In doing so, they found that NfL begins to increase between five to 10 years before cognitive decline begins and that the rate of change of serum NfL was a good predictor of cortical atrophy and decline on the Mini-Mental State Exam. These findings suggest that this test may be a marker of the neurodegenerative aspect of the disease in those at a high risk of developing AD.

Why It's Important: Although important advancements have been made in the development of diagnostic tests that are specific to AD and other associated dementias, the long time period from when amyloid-beta pathological changes begin to when cognitive decline starts introduces a large amount of uncertainty in predicting the likelihood of dementia on cognitively normal adults with abnormal AD biomarkers. Furthermore, the most accurate AD diagnostic biomarkers are either PET or cerebrospinal fluid (CSF)-based and therefore limit their use at this time.

As the ability to identify those at risk for AD improves it is important to determine reliable tests for determining those at the greatest risk of developing cognitive decline in the near future. Moreover, NfL has been shown to respond to disease-modifying therapies in multiple sclerosis, suggesting that it might also provide an important outcome measure of the neurodegenerative process in AD clinical trials.

Additionally, other studies have demonstrated that CSF and serum changes in NfL are highly correlated, indicating that a blood test is likely to be sufficient when using this as a diagnostic measure. Although there is plenty of work to be done, this study has been confirmed in non-familial forms of AD and NfL has become a measure of great focus in AD research and clinical trials.

The Pick: Largent EA, Terrasse M, Harkins K, et al. Attitudes toward physician-assisted death from individuals who learn they have an Alzheimer disease biomarker. JAMA Neurol 2019;76(7):864-866.

The Findings: In this small study of participants participating in the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study, a secondary prevention trial testing whether solanezumab can slow cognitive decline in persons with amyloid accumulation, and a related study, participants who had abnormal or normal amyloid PET scans were followed over a 12-month period to assess how knowing whether they have an abnormal amyloid level affected their views on physician-assisted death (PAD). Twelve months after they received the results of their abnormal amyloid PET scans, approximately 20 percent reported that they would consider PAD if they began to develop dementia or consider themselves a burden to others. Importantly, these participants in the study nonetheless endorsed a greater likelihood of planning for the future.

Why It's Important: Given the increasing push for prevention studies in Alzheimer's disease and the development of increasingly accurate and accessible diagnostic tests for AD related biomarkers, it is imperative that we understand the potential benefits and hazards of cognitively-normal adults learning about whether they have abnormal AD pathologies that significantly increase their risk for developing dementia. We have truly entered into a stage in AD research where the neurobiological underpinnings of the disease can be identified prior to the development of clinical impairment. Although this offers the opportunity for greater chances of identifying disease-modifying therapies, until there are effective preventive therapies it is absolutely critical that we understand how this type of information affects our patients.

JACQUELINE A. FRENCH, MD, FAAN

Professor of Neurology

NYU School of Medicine

New York, NY

The Pick: Lagae L, Sullivan J, Knupp K, et al for the FAiRE DS Study Group. Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A randomised, double-blind, placebo-controlled trial. Lancet 2019; 394(10216):2243-2254.

The Findings: This is the first randomized, placebo-controlled trial of fenfluramine for Dravet syndrome. A total of 119 children with Dravet syndrome were randomized to high- or low-dose fenfluramine, compared with placebo, and treated for 14 weeks. Convulsive seizures were reduced substantially. The high-dose group (0.7 mg/kg) had 62.3 percent greater reduction in mean monthly convulsive seizure frequency compared with those taking placebo; the low-dose group (0.2 mg/kg per day) showed a 32.4 percent reduction compared with those taking placebo. Half the children in the high-dose group and almost a quarter in the low-dose group had a 75 percent or greater reduction in mean monthly convulsive seizures. The drug was tolerable for most. There were no dropouts in the low-dose group; six dropped out in the high-dose group compared with three in the placebo group.

Why It's Important: There has been a greater focus on treatment of orphan epilepsies over the last decade. Dravet syndrome has been the orphan poster child, with numerous trials underway for the condition. Pharmaceutical-grade cannabidiol (Epidiolex) was the first antiseizure medication approved for Dravet syndrome. Based on the trial above, the US FDA recently granted fenfluramine a priority review. Such reviews are given to drugs that are expected to have a substantial impact on a disease. Fenfluramine is currently undergoing trials in Lennox-Gastaut syndrome, another orphan epilepsy. Safety studies are also ongoing, to ensure that the valve thickening and pulmonary fibrosis seen with Fen-Phenwhich had fenfluramine as a componentdo not occur.

Read the Neurology Today article, In the Pipeline-Oral Fenfluramine Is Promising Therapy for Children with Dravet Syndrome (January 9, 2020).

The Pick: Kapur J, Elm J, Chamberlain JM, et al, for the NETT and PECARN Investigators. Randomized trial of three anticonvulsant medications for status epilepticus. N Engl J Med 2019;381(22):2103-2113.

The Findings: This randomized trial assessed levetiracetam, fosphenytoin, and valproate for the treatment of status epilepticus, which continued after benzodiazepines had failed. The trial was stopped for futility after 384 adults and children were randomized. The endpoint of cessation of clinically-apparent status and improving mental status, without the addition of another medication at 60 minutes, was achieved in 47 percent of patients assigned to levetiracetam, 45 percent assigned to fosphenytoin, and 46 percent assigned to valproate. Adverse effects were similar between the groups.

Why It's Important: Status epilepticus is a major cause of harm related to seizures and epilepsy. Levetiracetam has increasingly been used in place of the older antiseizure medications phenytoin and valproate due to the perception that it is safer and produces less drug interactions. To date, there has been no rigorous evidence to support its use. This study shows no substantial difference (either in safety or efficacy) when levetiracetam is used, compared with the older drugs. Unfortunately, in the absence of a difference, it is impossible to say if any of the drugs were effective, however there is a reasonable likelihood that the status epilepticus did not stop on its own, considering that median time to seizure cessation after infusion was less than 15 minutes for all three drugs. The study highlights a very significant treatment gap, with fully half of patients inadequately treated with any of the three studied antiseizure medications.

Read the Neurology Today article, For Your Patients-Three Anticonvulsants Are Equally Effective for Status Epilepticus (January 9, 2020).

The Pick: Dubey D, Britton J, McKeon A, et al. Randomized placebo-controlled trial of intravenous immunoglobulin in autoimmune LGI1/CASPR2 epilepsy. Ann Neurol 2019;Epub 2019 Nov 28.

The Findings: Fourteen patients with LGI1- and three with CASPR2-related epilepsy who had two seizures per week were randomized to placebo versus treatment with IVIG added to standard antiseizure medicine. At baseline more than half of the patients were having 10 or more seizures daily. Six of eight patients in the IVIG group were responders (with a 50 percent reduction in seizures from baseline to five weeks), compared with two of nine in the placebo group (p=0.044). Only two patients treated with IVIG were seizure-free by the end of the study. The authors concluded that IVIG combined with antiseizure medicine is more effective than antiseizure medicine alone.

Why It's Important: There has been a great deal of interest in autoimmune epilepsy. When patients present with cognitive disturbance and a high seizure burden, the diagnosis is made more readily, but there may be additional patients who present as more typical focal epilepsy. This study underscores that the diagnosis is important and has treatment implications. While this study provides evidence that IVIG is superior to antiseizure medicines, the role of other standard immunotherapies such as corticosteroids and plasma exchange, either alone or in combination with IVIG, remains to be determined.

SHAWNIQUA WILLIAMS ROBERSON, MD

Assistant Professor of Neurology

Vanderbilt University Medical Center

Nashville, TN

The Pick: Kini LG, Bernabei JM, Mikhail F, et al. Virtual resection predicts surgical outcome for drug-resistant epilepsy. Brain 2019;142(12):3892-3905.

The Findings: This study combined automated processing of neuroimaging and intracranial EEG (iEEG) recordings in 28 patients with drug-resistant epilepsy to determine which specific brain regions, if resected, were most likely to result in seizure freedom. The authors found that decreases in broadband synchronizability of the resection zone at seizure-onset predicted surgical outcome (AUC 0.89, 95% CI 0.76-1.00) and that this information correctly predicts outcomes even when visual inspection of ictal iEEG could not clearly identify the seizure-onset zone. Preictal perilesional synchronizability was higher in nonlesional patients with malformations of cortical development than in those with lesions evident on MRI (rank sum statistic -2.08, p=0.04).

Why It's Important: Selection of surgical resection candidates and precise identification of the optimal extent of resection is the holy grail in the management of drug-resistant focal epilepsy. This study presents an important step forward, validating the previously published virtual resection method in a cohort of patients with and without identifiable MRI lesions and elucidating relationships between network synchronizability and certain clinical characteristics. Additionally, the authors provide a robust pipeline including rigorous clinical marking and validation of electrocorticographic recordings, MRI-based resection zone quantification, and online data-sharing. This open invitation to collaborate sets the stage for further advances to hone our prediction models and improve surgical resection planning for patients with intractable epilepsy.

The Pick: Ghassemi MM, Amorim E, Alhanai T, et al, for the Critical Care Electroencephalogram Monitoring Research Consortium. Quantitative electroencephalogram trends predict recovery in hypoxic-ischemic encephalopathy. Crit Care Med 2019;47(10):1416-1423.

The Findings: The authors compared several prediction models for prognostication of neurologic outcome (Cerebral Performance Category) at six months after cardiac arrest in a series of 438 patients across four institutions. They found that a model using time-varying quantitative EEG features collected over 72 hours outperformed a time-invariant model (p< 0.05) and other models, including a clinical prediction model and a random forest model.

Why It's Important: Accurate prognostication of outcomes after cardiac arrest remains an important and unsolved challenge for neurologists. This study introduces a novel methodologic approach to optimizing prognostication by capitalizing on the time-varying nature of quantitative EEG characteristics to optimize the weighting of each feature and timepoint in the model. This approach outperforms current state-of-the-art models, which use only static features, demonstrating that the statistical association between quantitative EEG features and neurologic outcome changes over time. This study paves the way for development of a risk score that further improves prognostication by incorporating both clinical and EEG features in a time-sensitive manner.

The Pick: Fultz NE, Bonmassar G, Setsompop K, et al. Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 2019;366(6465):628-631.

The Findings: This study investigated EEG, BOLD hemodynamics and CSF oscillations in the fourth ventricle during sleep in a series of 13 participants. They found a large amplitude, pulsatile flow of CSF at 0.05 Hz during non-REM sleep (5.52dB increase, 95%CI 2.33-7.67dB) and observed a strong anticorrelation between this signal and gray matter BOLD oscillations (r= -0.48 at lag 2s, p<0.001). They also found that the CSF pulsations were entrained to fluctuations in amplitude of the slow-delta EEG waves of non-REM sleep (peak amplitude=21%, p<0.001, shuffling).

Why It's Important: The mechanisms by which sleep can be restorative are poorly understood. CSF flow is thought to play a role by facilitating clearance of waste products during sleep. This study demonstrates that CSF flow is entrained by slow waves during non-REM sleep and suggests that the electrophysiological signatures of sleep may drive its physiologically-restorative effects. The study opens the way to further assessment of whether impaired CSF flow dynamics linked to slow-wave sleep lead to neurodegeneration, and whether strategies to preserve slow-wave sleep can rescue brain function.

Read the Neurology Today article, Disease Mechanisms-Slow Waves of CSF During Sleep Clear Toxins Linked to Neurodegenerative Conditions (December 5, 2019).

MICHAEL A. RUBIN, MD, MA, FAAN

Associate Professor of Neurology and Neurotherapeutics

UT Southwestern Medical Center

Dallas, TX

The Pick: Russell JA, Epstein LG, Greer DM, et al. Brain death, the determination of brain death, and member guidance for brain death accommodation requests: AAN position statement. Neurology 2019; Epub 2019 Jan 2.

The Findings: Through this position statement, the AAN endorses the Uniform Determination of Death Act that brain death occurs when, among other factors, the irreversible loss of all functions of the entire brain, including the brainstem, has been demonstrated by complete loss of consciousness (coma), brainstem reflexes, and the independent capacity for ventilatory drive (apnea), in the absence of any factors that imply possible reversibility. The statement helps provide guidance to AAN members who encounter resistance to brain death, its determination, or requests for accommodation, including continued use of organ support technology despite neurologic determination of death.

Why It's Important: The frequency of controversial cases in determination of death by neurologic criteria has accelerated in the last few years. This paper is a first step in not only reiterating established criteria, but also offering Academy members advice in how to navigate the complex landscape that is developing nationally.

Read the Neurology Today story, Policy and Practice-Dead in California, Alive in New Jersey. Neurologists Seek Nationwide Consistency in Policies for Determining Brain Death (January 9, 2020).

The Pick: Vrselija Z, Daniele SG, Silbereis J, et al. Restoration of brain circulation and cellular functions hours post-mortem. Nature 2019; 568:336-343.

The Findings: The study described the restoration and maintenance of microcirculation and molecular and cellular functions of the intact pig brain under ex vivo normothermic conditions up to four hours post-mortem.

Why It's Important: This groundbreaking paper shows that interruption in blood flow and delivery of oxygen to an animal model brain for several hours may not lead to complete loss of cellular function of brain tissue, but likely still leads to loss of tissue and organ function. These data suggest that efforts for brain resuscitation ought to be continued in the acute setting of an injury before a definitive prognosis is determined.

Read the Neurology Today story, At the Bench-What the Post-Mortem Pig Brain Study Really Says About Brain Death (June 6, 2019).

JENNIFER BICKEL, MD, FAAN

Professor of Pediatrics

Children's Mercy Hospital

University of Missouri-Kansas City

Kansas City, MO

The Picks: Seng EK, Singer AB, Metts C, et al. Does mindfulness-based cognitive therapy for migraine reduce migraine-related disability in people with episodic and chronic migraine? A phase 2b pilot randomized clinical trial. Headache 2019; 59(9):1448-1467.

Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the treatment of migraine. N Engl J Med 2019;381(23)2230-2241.

Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist for migraine. N Engl J Med 2019;381(2):142-149.

Goadsby PJ, Wietecha LA, Dennehy EB, et al. Phase 3 randomized, placebo-controlled, double-blind study of lasmiditan for acute treatment of migraine. Brain 2019;142(7):1894-1904.

The Findings: In the Headache trial, 60 patients who had six to 30 headache days per month were randomized to either eight weekly individual mindfulness-based interventionsmindfulness mediation and cognitive-behavioral skillsor eight weeks of waitlist/treatment as usual. The mindfulness-based cognitive therapy effectively reduced headache-related disability and attack-level migraine related disability.

In the New England Journal of Medicine study on rimegepant, 1,672 participants were randomized to placebo and/or 50 mg of ubrogepant and 100 mg of ubrogepant. A higher percentage of participants who received ubrogepant had freedom from pain and absence of the most bothersome symptomnausea, somnolence, and dry mouthat two hours after the dose.

The New England Journal of Medicine study of lasmiditan randomized 1,186 patients to rimegepant or placebo; the percentage of patients who were free from their most bothersome symptom was 37.6 percent for the rimegepant group compared with 25.2 percent in the placebo group (p<0.001).

The Brain study reported that in a prospective, double-blind, phase 3 multicenter study, lasmiditan, a serotonin 5-HT1F receptor agonist, was effective for acute treatment of patients with migraine. A total of 3,005 patients with migraine were randomized to oral lasmiditan 200 mg, 100 mg, 50 mg, or placebo. Lasmiditan was associated with significantly more pain freedom at two hours200 mg (p<0.001); 100 mg (p<0.001); 50 mg (p=0.003) versus placebo.

Why It's Important: 2019 was another great year for advances in headache management. We have seen FDA approval for novel pharmaceutical options, including ubrogepant and lasmiditan, as well as for additional neurostimulator options. In addition, research continues to indicate that non-pharmaceutical treatments such as mindfulness-based cognitive therapy can significantly reduce migraine related disability. As a Headache Section Chief, I have overseen the care of tens of thousands of patients with refractory, disabling headaches. Never before have we headache specialists had so many options to offer our patients. It's truly exciting to see how far the field has come since I entered practice almost 15 years ago.

Read the Neurology Today article, In the Pipeline-Rimegepant Is Effective for Acute Migraine Pain at 2 Hours, Study Finds (August 8, 2019).

The Pick:The National Academy of Medicine Action Collaborative on Clinician Well-Being and Resilience

The Finding: The NAM Collaborative on Clinician Well-Being and Resilience has brought together a network of 60 organizations to raise the visibility of clinician anxiety, burnout, depression, stress and suicide; improve baseline understanding of challenges to clinician well-being; and advance evidence-based, multidisciplinary solutions to improve patient care by caring for the caregiver. Neil A. Busis, MD, FAAN, a member of the Neurology Today editorial board, represents neurology in this ambitious initiative. The collaborative has sponsored initiatives around wellness, including several that have been featured in Neurology Today this year.

Why It's Important: New FDA approvals like those featured above for migraine are not enough to help our patients and our field. We need major changes in our field to return to the core values of humanism and professionalism in medicine. The National Academy of Medicine Action Collaborative on Clinician Well-being is playing a major role in supporting that goal.

Read the Neurology Today article, Wellness: A National Initiative to Build a Hub for Wellness Resources (March 7, 2019).

MELISSA J. NIRENBERG, MD, PHD, FAAN

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