Category Archives: Gene Medicine

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to vutrisiran, an investigational therapeutic for the treatment of the polyneuropathy of hereditary transthyretin-mediated (hATTR) amyloidosis in adults. According to the FDA, Fast Track designation is designed to facilitate the development and expedite the review of drugs that treat serious conditions and fill an unmet medical need. With this designation, Alnylam will be eligible to submit a rolling New Drug Application for vutrisiran.

Vutrisiran has demonstrated an encouraging safety profile in the Phase 1 study, with infrequent quarterly dosing with low-volume, subcutaneous administration which potentially reduces the burden of care for this progressive, life-threatening and multisystem disease. We are therefore pleased that the FDA has granted vutrisiran Fast Track designation, said Rena Denoncourt, Vutrisiran Program Leader at Alnylam. After completing enrollment earlier this year, we look forward to sharing topline results of the HELIOS-A Phase 3 study of vutrisiran in early 2021. More broadly, we remain committed to developing additional therapeutic options for the treatment of ATTR amyloidosis to augment the market-leading position of ONPATTRO (patisiran), approved for the treatment of the polyneuropathy of hATTR amyloidosis in adults.

In addition to Fast Track designation, vutrisiran has been granted Orphan Drug designation in the United States and the European Union for the treatment of ATTR amyloidosis. The safety and efficacy of vutrisiran are being evaluated in the ongoing HELIOS-A and HELIOS-B Phase 3 clinical trials. Together, these studies comprise a comprehensive clinical development program intended to demonstrate the broad impact of vutrisiran across the multisystem manifestations of disease and the full spectrum of patients with ATTR amyloidosis.

About Vutrisiran Vutrisiran is an investigational, subcutaneously-administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hereditary (hATTR) and wild-type (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, blocking the production of wild-type and mutant transthyretin (TTR) protein before it is made. Quarterly administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylams next-generation delivery platform known as the Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency or any other health authority.

About HELIOS-A Phase 3 Study HELIOS-A is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran in patients with hATTR amyloidosis with polyneuropathy. The trial randomized patients 3:1 to receive either 25mg of vutrisiran subcutaneously once every 12 weeks or 0.3 mg/kg of patisiran intravenously once every three weeks. For most endpoints, results from the vutrisiran arm will be compared to results from the placebo arm of the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in people with hATTR amyloidosis with polyneuropathy. The co-primary endpoints of HELIOS-A are the change from baseline in the modified Neurologic Impairment Score +7 (mNIS+7) and in the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QoL-DN) score, at 9 months. Secondary endpoints include the change from baseline in key clinical evaluations including the timed 10-meter walk test (10-MWT), modified body mass index (mBMI), and Rasch-built Overall Disability Scale (R-ODS). The percent reduction in serum transthyretin (TTR) levels in the vutrisiran arm will be compared to the within-study patisiran arm. Additional exploratory endpoints will be assessed to determine the effect of vutrisiran on other aspects of the multisystem nature of this disease, including manifestations of cardiac amyloid involvement.

About HELIOS-B Phase 3 Study HELIOS-B will evaluate the efficacy of vutrisiran versus placebo toward the composite outcome of all-cause mortality and recurrent cardiovascular hospitalizations at 30 months, the primary study endpoint. The study protocol includes an optional interim analysis to be conducted at the Companys discretion. HELIOS-B complements the ongoing HELIOS-A Phase 3 study in patients with hereditary ATTR amyloidosis with polyneuropathy, creating a comprehensive clinical development program to evaluate the safety and efficacy of vutrisiran across the entire disease spectrum of ATTR amyloidosis.

ONPATTRO Important Safety Information Infusion-Related Reactions Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO (patisiran). In a controlled clinical study, 19% of ONPATTRO-treated patients experienced IRRs, compared to 9% of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory tract infections (29%) and infusion-related reactions (19%).

Indication ONPATTRO is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

For additional information about ONPATTRO, please see the full Prescribing Information.

About Transthyretin (ATTR) Amyloidosis Transthyretin (ATTR) amyloidosis is a rare, progressively debilitating, and fatal disease caused by misfolded TTR proteins that accumulate as amyloid deposits in multiple tissues including the nerves, heart and gastrointestinal (GI) tract. There are two types of ATTR amyloidosis: hereditary ATTR (hATTR) amyloidosis and wild-type (wtATTR) amyloidosis. hATTR amyloidosis is an inherited disease resulting in intractable peripheral sensory-motor neuropathy, autonomic neuropathy, and/or cardiomyopathy. It is estimated to affect 50,000 people worldwide. The condition can have a debilitating impact on a patients life and may lead to premature death within 4.7 years of diagnosis. wtATTR amyloidosis is a nonhereditary, progressive type of the disease with undefined etiology. It affects an estimated 200,000-300,000 people worldwide. It primarily manifests as cardiomyopathy, which leads to heart failure and mortality within 2 to 6 years.

About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as a major scientific breakthrough that happens once every decade or so, and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of todays medicines by potently silencing messenger RNA (mRNA) the genetic precursors that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

About Alnylam Alnylam (Nasdaq: ALNY) is leading the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare genetic, cardio-metabolic, hepatic infectious, and central nervous system (CNS)/ocular diseases. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach for the treatment of a wide range of severe and debilitating diseases. Founded in 2002, Alnylam is delivering on a bold vision to turn scientific possibility into reality, with a robust RNAi therapeutics platform. Alnylams commercial RNAi therapeutic products are ONPATTRO (patisiran), approved in the U.S., EU, Canada, Japan, Switzerland and Brazil, and GIVLAARI (givosiran), approved in the U.S. and EU. Alnylam has a deep pipeline of investigational medicines, including five product candidates that are in late-stage development. Alnylam is executing on its "Alnylam 2020" strategy of building a multi-product, commercial-stage biopharmaceutical company with a sustainable pipeline of RNAi-based medicines to address the needs of patients who have limited or inadequate treatment options. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit http://www.alnylam.com and engage with us on Twitter at @Alnylam or on LinkedIn.

Forward Looking Statements Various statements in this release, including, without limitation, Alnylam's views and plans with respect to the potential for RNAi therapeutics, including vutrisiran, its expectations with respect to the encouraging safety profile of vutrisiran in the Phase 1 study, timing for reporting topline results from its HELIOS-A Phase 3 study, its commitment to developing multiple therapeutic options for the treatment of ATTR amyloidosis, the intended goals of the HELIOS-A and -B studies to demonstrate the broad impact of vutrisiran across the multisystem manifestations of disease and the full spectrum of patients with ATTR amyloidosis, and expectations regarding the continued execution on its Alnylam 2020 guidance for the advancement and commercialization of RNAi therapeutics, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: potential risks to Alnylams business, activities and prospects as a result of the COVID-19 pandemic, or delays or interruptions resulting therefrom; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates, including vutrisiran; the pre-clinical and clinical results for its product candidates, which may not be replicated or continue to occur in other subjects or in additional studies or otherwise support further development of product candidates for a specified indication or at all; actions or advice of regulatory agencies, which may affect the design, initiation, timing, continuation and/or progress of clinical trials or result in the need for additional pre-clinical and/or clinical testing; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; intellectual property matters including potential patent litigation relating to its platform, products or product candidates; obtaining regulatory approval for its product candidates, including inclisiran and lumasiran, and maintaining regulatory approval and obtaining pricing and reimbursement for its products, including ONPATTRO and GIVLAARI; progress in continuing to establish a commercial and ex-United States infrastructure; successfully launching, marketing and selling its approved products globally, including ONPATTRO and GIVLAARI, and achieve net product revenues for ONPATTRO within our expected range during 2020; Alnylams ability to successfully expand the indication for ONPATTRO in the future; competition from others using technology similar to Alnylam's and others developing products for similar uses; Alnylam's ability to manage its growth and operating expenses within the ranges of our expected guidance and achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylams ability to establish and maintain strategic business alliances and new business initiatives; Alnylam's dependence on third parties, including Regeneron, for development, manufacture and distribution of certain products, including eye and CNS products, and Ironwood, for assistance with the education about and promotion of GIVLAARI; the outcome of litigation; the risk of government investigations; and unexpected expenditures, as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) and in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements.

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Alnylam Receives Fast Track Designation for Vutrisiran for the Treatment of the Polyneuropathy of hATTR Amyloidosis - BioSpace

TORONTO & SINGAPORE--(BUSINESS WIRE)--Cyclica announces a multi-year and multi-project collaboration with the Genome Institute of Singapore (GIS), a research institute under the Agency for Science, Technology and Research (A*STAR). Cyclica and GIS will carry out research efforts spanning from polypharmacology profiling to novel compound design for diverse drug discovery programs in oncology and related diseases. The collaboration will leverage GIS deep expertise in functional genomics, drug target discovery, and data analytics, and Cyclicas AI-augmented and proprietary, Ligand Design and Ligand Express platform.

The world-class team of scientists at GIS will conduct new compound design and off-target profiling to discover hits and subsequently develop the lead compounds. GIS will perform functional analyses and testing of compounds derived from Cyclicas drug discovery platform against gene targets of interest to GIS. This cross-border collaboration provides a unique opportunity to tailor drug identification and development efforts in a holistic way that will enable the advancement of precision medicine. By empowering researchers and healthcare institutes who are at the forefront of innovation, Cyclica and GIS will pave the way to decentralize the drug discovery process and develop the next generation of improved treatments for patients based on the individuals disease features.

Dr. Tam Wai Leong, Group Leader of Precision Oncology at GIS, said, Applying AI-augmented approaches towards drug design is innovative and forward-looking. It has the potential to rapidly grow the arsenal of new drugs in our fight against diseases like cancer, especially in an era of genomic medicine where physicians and scientists can better define the underlying genetic and molecular drivers of cancers.

Professor Liu Jianjun, Deputy Executive Director at GIS, added, Our ability to harness advanced genomic technologies has enhanced our discovery of genetic contributions to a spectrum of diseases, including cancer. Many of these important cancer drivers currently do not have drugs that target them. We believe that machine learning and deep learning models will shorten the time and cost for the development of new therapeutics, and are pleased to collaborate with Cyclica to further our efforts in developing therapeutics that can have a positive impact on patients.

The calibre of genomic research at GIS is world-class. We are thrilled to have the opportunity to work with many leading scientists at GIS to innovate novel therapeutics, based on genomic discoveries, for a wide range of diseases. This opportunity to make a meaningful contribution and impact to patients are common values we share with our partners at GIS, said Dr. Verner De Biasi, VP, Global Head of Strategic Partnerships at Cyclica.

About Cyclica, Inc. (Cyclica)

Cyclica is a Toronto, Canada based biotechnology company that is decentralizing the discovery of new medicines with its integrated structure-based and AI-augmented drug discovery platform, Ligand Design and Ligand Express. Taken together Ligand Design and Ligand Express design advanced lead-like molecules that minimize unwanted off-target effects, while providing a holistic understanding of a molecule's activity through integrated systems biology and structural pharmacogenomics. Cyclicas differentiated platform opens new opportunities for drug discovery, including multi-targeted and multi-objective drug design, lead optimization, ADMET-property prediction, target deconvolution, and drug repurposing for a wide range of indications. With a world-class team with deep roots in industry and a first-in-class integrated drug discovery platform, Cyclica will spark a surge of innovation through a combination of venture creation and partnerships with early-stage and emerging biotech companies. By doing more with AI, Cyclica will revolutionize a system troubled with attrition and costly failures, accelerate the drug discovery process, and develop medicines with greater precision.

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Cyclica Forms Multi-Year and Multi-Project Drug Discovery Partnership with the Genome Institute of Singapore - Business Wire

GAITHERSBURG, Md., April 14, 2020 (GLOBE NEWSWIRE) -- OpGen, Inc. (Nasdaq: OPGN, OpGen), a precision medicine company harnessing the power of molecular diagnostics and informatics to help combat infectious disease, announced today that total revenue for the first quarter of 2020 was approximately $617,000 down from $1.0 million in the first quarter of 2019, excluding revenues from the Curetis businesses, which was acquired upon closing of the business combination on April 1, 2020. Cash as of March 31, 2020 was approximately $11.5 million, up significantly from the $2.7 million as of December 31, 2019.

The company also announced accomplishment of the following key milestones, including key business milestones achieved by Curetis and Ares Genetics in the first quarter of 2020:

OpGen revenue during the first quarter of 2020 can be attributed to Acuitas AMR Gene Panel and Acuitas Lighthouse revenue, which was approximately $254,000, while revenues from the companys rapid FISH products decreased to $363,000. The company expects to provide full first quarter 2020 financial results during its first quarter 2020 earnings call in early May of this year.

Oliver Schacht, President and CEO of OpGen commented, In light of the unprecedented crisis situation with COVID-19, we were pleased with the robust first quarter 2020 initial results. We have been humbled and extremely encouraged by the dedication and hard work put in place by all our employees globally during these extraordinary times. Going forward and once this crisis is behind us, we anticipate dynamic growth in our business trajectory following the expected near-term FDA clearance decision of our Acuitas AMR Gene Panel. We also expect the CoV-2 test kit sales in Europe to continue contributing to our top-line revenue in Q2 of 2020.

Schacht continued, Now operating as one combined company, OpGen with its group companies Curetis and Ares Genetics boast strong proprietary assets for developing and commercializing innovative, data-driven solutions in infectious disease diagnostics, and we look forward to the continued integration of our businesses over the coming weeks and months.

The preliminary financial results are estimates prior to the completion of OpGensfinancial closing procedures and review procedures by its external auditors and therefore may be subject to adjustment when the actual results are available.

About OpGen, Inc.

OpGen, Inc. (Gaithersburg, MD, USA) is a precision medicine company harnessing the power of molecular diagnostics and bioinformatics to help combat infectious disease. Along with subsidiaries, Curetis GmbH and Ares Genetics GmbH, we are developing and commercializing molecular microbiology solutions helping to guide clinicians with more rapid and actionable information about life threatening infections to improve patient outcomes, and decrease the spread of infections caused by multidrug-resistant microorganisms, or MDROs. OpGens product portfolio includes Unyvero, Acuitas AMR Gene Panel and Acuitas Lighthouse, and the ARES Technology Platform including ARESdb, using NGS technology and AI-powered bioinformatics solutions for antibiotic response prediction.

For more information, please visit http://www.opgen.com.

Forward-Looking Statements

This press release includes statements regarding the pursuit of FDA clearance for the Acuitas AMR Gene Panel for use with bacterial isolates, the integration of OpGen with its acquired subsidiaries, Curetis GmbH and Ares Genetics GmbH, and activities related to the companys products and services. These statements and other statements regarding OpGens future plans and goals constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934 and are intended to qualify for the safe harbor from liability established by the Private Securities Litigation Reform Act of 1995. Such statements are subject to risks and uncertainties that are often difficult to predict, are beyond our control, and which may cause results to differ materially from expectations. Factors that could cause our results to differ materially from those described include, but are not limited to, our ability to successfully, timely and cost-effectively develop, seek and obtain regulatory clearance for and commercialize our product and services offerings, the rate of adoption of our products and services by hospitals and other healthcare providers, the realization of expected benefits of our business combination transaction with Curetis GmbH, the success of our commercialization efforts, the effect on our business of existing and new regulatory requirements, and other economic and competitive factors. For a discussion of the most significant risks and uncertainties associated with OpGen's business, please review our filings with the Securities and Exchange Commission. You are cautioned not to place undue reliance on these forward-looking statements, which are based on our expectations as of the date of this press release and speak only as of the date of this press release. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise.

OpGen:Oliver SchachtPresident and CEOInvestorRelations@opgen.com

OpGen Press Contact:Matthew BretziusFischTank Marketing and PR matt@fischtankpr.com

OpGen Investor Contact:Joe Green Edison Groupjgreen@edisongroup.com

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OpGen Announces Preliminary Unaudited Revenue and Cash Position for First Quarter 2020 and Provides Business Update - GlobeNewswire

In Conversation provides a glimpse into the life of an outlier an exceptional person going above and beyond to improve outcomes in their field. In 2019, Professor Kathryn North AC won the prestigious Peter Wills Medal Research Australias flagship award in recognition of her outstanding leadership in genomic medicine, which has helped drive Australias international reputation in this field.

As Director of the Murdoch Childrens Research Institute, Professor North plays a key role in integrating genomic testing and diagnosis into standard health care, with the aim to shorten diagnosis times and increase diagnostic rates to enable early intervention as well as provide access to treatment for people with genetic disorders and cancer. Through her own research, she has worked to identify new disease genes and improve diagnosis, setting the benchmark for ongoing research efforts.

This award, which Im incredibly thrilled to receive, really recognises a range of roles Ive played not just as an individual researcher but as part of the efforts of hundreds of researchers in Australia and around the world working together to bring advanced genomics into standard health care.

After training as a child neurologist, I became increasingly fascinated by genetics and its potential to predict, diagnose and help treat disease. The lure of research drew me back to the lab, with a major focus on inherited muscle diseases like muscular dystrophy, which can lead to lifelong disability in affected children and adults. My work in this area led me to discover the effects of the gene ACTN3, which influences muscle power and recovery from damage and was subsequently dubbed the gene for speed.

We studied elite athletes and demonstrated that ACTN3 is a major determinant of skeletal muscle performance, but my team has also recently shown that variations in ACTN3 influence disease severity and progression in Duchenne muscular dystrophy. We are now studying how it influences muscle-wasting associated with ageing, steroid use and cancer.

My research is just one example of how genomic medicine can make a tremendous difference. This led me to help establish Australian Genomics, a national network of clinical and laboratory genetics services, hospitals, universities, research institutions and patient advocacy groups working together to establish procedures to enable all Australians access to genomic health care. The Murdoch Childrens Research Institute is now at the forefront of the genomics revolution, translating the latest discoveries into clinical practice.

An accurate diagnosis is hugely important because it gives answers to both the patient and the clinician. In my work as a paediatrician, Ive seen parents desperately seeking an answer to the cause of their kids intellectual or physical disability, wanting to know about their childs future and whether they would have other affected children.

Previously, we just couldnt answer these questions. Advances in genetic technology mean all genes can now be sequenced quickly and cheaply, and the information used to predict, diagnose and treat rare diseases as well as many forms of cancer.

Medical genetics and genomics has changed dramatically since the mid 90s. In the past we were able to give families with affected children a clinical description, but couldnt accurately put a label on what exactly was wrong.

The Human Genome Project and the development and rollout of advanced next-generation, ultrarapid gene sequencing have been an absolute game changer. I couldnt have imagined that wed be using genome technologies in the clinic within two years of using it in a research setting, increasing the diagnostic rate fivefold, and having geneticists working side by side with intensive care physicians to provide that diagnosis within three days.

We can now provide a genetic diagnosis for 50 to 90% of our families and answer these difficult questions.

Genomics is absolutely going to transform healthcare delivery. Using global data gathered and shared responsibly from millions of people, we can be much more accurate in making a prediction about the individual. We will be able to move to a healthcare model of prediction, prevention, early intervention and targeted treatment, and eventually improve and maintain the wellness of the population rather than focusing solely on illness.

This will no doubt come with significant challenges. To overcome these we need to approach genomics at the local and national level, and partner globally to be able to apply our insights to individuals accurately and with meaning.

Its incredibly important we engage at a public level so the community can understand our work. We need to bring the public along on this journey and explain the applications and great benefits of applying big data and genomic technologies to benefit individual patients. Its up to us as doctors and researchers to convey those messages accurately, strongly and with a united voice.

Research Australias Health and Medical Research Awards are important because they increase the visibility of science in general and medical research in particular within the community. They bring recognition to the researchers behind some of Australias most exciting medical and health discoveries, and kickstart conversations we need to be having to harness the possibilities of science for community benefit.

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In Conversation with Professor Kathryn North - Australian Hospital + Healthcare Bulletin

By Jennifer Couzin-FrankelApr. 9, 2020 , 11:35 AM

In college in the 1990s, Alix Timko wondered why she and her friends didnt have eating disorders. We were all in our late teens, early 20s, all vaguely dissatisfied with how we looked, says Timko, now a psychologist at Childrens Hospital of Philadelphia. Her crowd of friends matched the profile she had seen in TV dramasoverachievers who exercised regularly and whose eating was erratic, hours of fasting followed by a huge pizza.

My friends and I should have had eating disorders, she says. And we didnt.

It was an early clue that her understanding of eating disorders was off the mark, especially for the direst diagnosis of all: anorexia nervosa. Anorexia is estimated to affect just under 1% of the U.S. population, with many more who may go undiagnosed. The illness manifests as self-starvation and weight loss so extreme that it can send the body into a state resembling hibernation. Although the disorder also affects boys and men, those who have it are most often female, and about 10% of those affected die. Thats the highest mortality rate of any psychiatric condition after substance abuse, on par with that of childhood leukemia. With current treatments, about half of adolescents recover, and another 20% to 30% are helped.

As a young adult, Timko shared the prevailing view of the disease: that it develops when girls, motivated by a culture that worships thinness, exert extreme willpower to stop themselves from eating. Often, the idea went, the behavior arises in reaction to parents who are unloving, controlling, or worse. But when Timko began to treat teens with anorexia and their families, that narrative crumbledand so did her certainties about who is at risk. Many of those young people dont have body dissatisfaction, they werent on a diet, its not about control, she found. Their mom and dad are fabulous and would move heaven and Earth to get them better.

Timko wasnt alone. Other researchers were also questioning psychological theories of anorexia that had reigned for generations. Hunger is a basic drive, says Cynthia Bulik, a clinical psychologist who runs eating disorder centers at the University of North Carolina, Chapel Hill, and at the Karolinska Institute. The idea that patients use willpower to override hunger never rang true, she says. My patients have said for years that when they starve, they feel better. She began to consider another possibility: What if their biology is driving them to eschew food?

Bulik and Timko are now part of a small band of researchers working to untangle the biology of anorexia. The more they look, the more they find to suggest the diseases biological roots run deep. For instance, genetic studies indicate its about as heritable as obesity or depression. The circuitry of the brains reward system behaves differently in unaffected volunteers than in people with anorexia and those who have recovered. And new treatments drawing on biology are being tested, including deep-brain stimulation and psychedelic drugs. Those experiments aim not only to improve the outlook for patients, but also to explore how closely the disease aligns with others across psychiatry, including obsessive-compulsive disorder (OCD) and addiction.

Scientists pursuing those new ideas face a challenge, in part because of money: For fiscal year 2019, anorexia got $11 million in funding from the National Institutes of Health (NIH), a figure that hasnt changed notably in many years and that researchers decry as shockingly low given the diseases burdens. By contrast, schizophreniawhich has a similar prevalence and also surges during adolescencegarnered $263 million. The dearth of funder interest, many say, springs from the view that anorexias roots are cultural, along with shame and stigma still clouding the disease. But evidence is mounting that biology is at its core.

Many researchers lament that eating disorders, including anorexia nervosa, are underfunded given their prevalence. These numbers are drawn from 2017 data for the United States; the number of individuals affected is an estimate.

(GRAPHIC) X. LIU/SCIENCE; (DATA) BRYN AUSTIN/BOSTON CHILDRENS HOSPITAL; NATIONAL INSTITUTES OF HEALTH

Lori Zeltser pivotedto anorexia from studying obesity. A developmental neuroscientist at Columbia University, she studied the brains of developing mice, trying to identify feeding circuits that increase susceptibility to obesity in adulthood. Then about 10 years ago, Zeltser saw a notice for funding from the Klarman Family Foundation, formed by hedge fund manager Seth Klarman and his wife, Beth, now the foundations president. The foundation wanted to stimulate basic research into eating disorders, and because of Zeltsers research on appetite, she submitted a proposal.

To get up to speed on anorexia, Zeltser turned to the literature. Researchers in Sweden and Minnesota had compared anorexia rates in identical and fraternal twins, a common approach to tease out heritability of complex traits and diseases. Those reports showed that 50% to 60% of the risk of developing anorexia was due to genes, implying DNA is a powerful driver. By contrast, family studies suggest the heritability of breast cancer is about 30%, and that of depression is roughly 40%. I was shocked, Zeltser says.

Layered on the genetics work was a data point that caught Zeltsers attention. An antipsychotic drug, olanzapine, which causes profound weight gain as a side effect, had little to no effect on weight when tested in people with anorexia. Something in peoples biology prevented olanzapine from causing weight gain, Zeltser believes. That is not just [mental] control.

But a deep schism remains, with many practitioners concerned that biology is getting more attention than it deserves. If I had to choose nature versus nurture in the development of anorexia and other eating disorders, I would choose nurture, says Margo Maine, a psychologist who has treated eating disorders for years. Eating disorders are primarily female, she says, in part because gender is a cultural experience.

Psychotherapist Carolyn Costin, who recovered from anorexia in the late 1970s and established a network of private treatment centers around the United States, says biology plays a role but that cultural messages and psychological stressors are also important factors. She worries especially that the way biology research is described could discourage patients about their prospects for recovery. About 8 years ago, she says, Clients started coming in, saying, Its genetic, why bother trying to get well?

Such comments agitate researchers like Bulik. The patients she treats, she says, are reassured, not distressed, to learn that the disorder is rooted in biology and that biology doesnt translate into destiny. Although she, Zeltser, and others agree that anorexia has environmental drivers, as most chronic conditions do, they object to the idea that environment leads the way. Exposure to this ideal [of thinness] is ubiquitous, but everybody doesnt get anorexia nervosa, Bulik says. None of the sociocultural literature has ever been able to explain why. She adds, A lot of patients will say, It was never about being thin for me, ever.

If you look at psychiatric syndromes over 200 years, anorexia hasnt changed at all, whereas our culture has, says James Lock, a child psychiatrist who heads the child and adolescent eating disorders program at Stanford University School of Medicine.

To begin digging into the biology of anorexia, Zeltser used a 2010 grant from the Klarman foundation to build a mouse model of the disease. Because feeding is easy to measure, she reasoned that anorexias restrained feeding behavior is well-suited for animal modeling. Her goal was to study the eating and starvation patterns of the mice and explore how genetics and the environment interact to trigger the disorder.

In a 2016 issue ofTranslational Psychiatry,Zeltser described micewith a variant in a gene that in people is linked to anorexia. On its own, the variant didnt noticeably affect mouse feeding behavior. To mimic the pullback from eating that often precedes a diagnosis, the researchers restricted the animals caloric intake by 20% to 30%. Then they induced stress, another factor linked to anorexia, by housing the normally social animals alone. The result: The mice stop eating, Zeltser says.

Lori Zeltser, a developmental neuroscientist at Columbia University, has developed a mouse model of anorexia nervosa.

Zeltser is talking with clinical colleagues about comparing her rodents behavior with videos of patients in a feeding lab, where researchers observe how much people eat, which nutrients they choose, and which they avoid. If the behaviors seem parallel, the mice could help point the way to new treatments or even different environments that could better support eating.

But publishing her animal work has proved difficult. Zeltser is often asked, How do you know if what youre finding is relevant to humans? Thats a common question of anyone doing mouse work, but Zeltser says the challenge here runs deeper. This is not taken seriously as a disease that has a biological basis, she says. Instead, its dismissed as extreme girl behavior and oh my God, theyre crazy, pushback she finds immensely frustrating.

Accumulating genetic data could change that by making anorexias biological roots harder to ignore. Some of the strongest evidence emerged last summer, when Bulik and others published inNature Geneticsthe largest genetics study on the disease, with roughly $9 million in funding from the Klarman foundation and additional funds from NIH. By analyzing the genomes of nearly 17,000 people with anorexia and more than 55,000 people without, the researchers identified eight statistically significant genomic regions, along with other patterns of genetic associations that yielded important clues. Some of those associations tracked with results of studies of other psychiatric illnesses, including OCD and depression, which didnt surprise Bulik. What did were overlapping associations with DNA controlling body mass index (BMI), lipids, and other metabolic traits.

We said, This doesnt look like any other psychiatric disorder, Bulik says. It might be the inverse of obesitythese people might be genetically predisposed to low BMI. In the February 2019 issue of theJournal of the American Academy of Child & Adolescent Psychiatry, she and her teamsifted through BMI recordsfor young people later diagnosed with anorexia and other eating disorders. The BMIs of 243 people diagnosed with anorexia began to diverge from those of a control group before they started kindergarten.

Bulik is now launchingthe Eating Disorders Genetics Initiative, with more than $7 million from NIH, additional funding from Sweden and the United Kingdom, and potential infusions from other countries and individual donors. The initiative aims to include 100,000 people with anorexia nervosa, bulimia nervosa, and binge eating disorder. Although genetics is unlikely to offer quick solutions, Bulik hopes it can shine the light in the direction you need to go for effective therapies, including medications.

The genetic findingsmight one day intersect with another line of research: studies of brain structures and signaling that are revealing tantalizing differences between people with and without anorexia. At Columbia, psychiatrist Joanna Steinglass wanted to understand how the brains of people with anorexia guide their food choices. In two studies, she and her colleagues recruited inpatients with eating disorders along with a control group. In people with anorexia, both during and after hospitalization, MRI scans showed the region of the brain associated with selecting foods was the dorsal striatum, which is key to forming habits. In people without an eating disorder, a different brain region guides choices. The work first appearedin 2015 inNature Neuroscience, and the team presented more findings at a conference last year.

Theyre using different circuits when they make decisions, Steinglass says. This jibes with her idea that as people repeatedly restrict eating, the behavior moves to a different brain region and becomes less amenable to change. That could help explain why many recovered patients relapse.

Another clue to how the brain might throw eating off trackwas reported last month inThe American Journal of Psychiatry. Walter Kaye, a psychiatrist who directs the eating disorders program at the University of California (UC), San Diego, led a study looking at how the brains of people with anorexia behave when their bodies are hungry. Kaye, whose program treats about 70 patients per day, ran a study that included 48 women, 26 of whom had anorexia. Each was studied twice with brain imaging, once immediately after a meal and, on a separate visit, after fasting for 16 hours.

Kaye knew hunger activates brain circuits that in turn motivate eating, making food desirable. That relationship was clear during brain imaging of the control group volunteers: When they were offered sugar water after 16 hours of fasting, their reward and motivation circuits lit up. But in people with anorexia, those circuits were much less active after fasting. They could identify being hungry, Kaye says, but their brains couldnt convert that into a desire to eat. The patients also experienced heightened anxiety and inhibition, along with diminished reward signaling in their brains. That effect may further impair their drive to eat. Kaye suggests people with anorexia miscode food as risky rather than rewarding.

A lot of patients will say, It was never about being thin for me, ever.

Psychiatrist Rebecca Park at the University of Oxford also suspects the disease hijacks the brains reward system. Some of her patients experience this sense of aberrant reward, almost a high from starvation, she says. Parks neuroscience research indicates aberrant brain responses to reward cues.

Are those brain differences a cause or a result of starvation? Studying people in remission eliminates the effects of malnutrition on the brain but cant definitively answer the question. Its likely that starvation in adolescence is going to damage your brain, Park says. One way to begin to disentangle whether the brain differences predate the disease is to study people very early in its course. Steinglass is in the third year of a brain scanning study of reward circuitry, which now includes 55 recently diagnosed teenagers and a control group of 25 others. The coronavirus pandemic has halted enrollment for now, but Steinglass hopes to have results in 2 to 3 years. Other researchers are working to understand how, and to what degree, the brain recovers once eating resumes.

Theres an overall sensethat were joining the rest of the world by finally applying scientific methods to anorexia nervosa, Steinglass says. The ultimate goal is new treatments, which are sorely needed.

The most studied and most effective strategy to date is called family-based treatment (FBT), which originated at the Maudsley Hospital in London. It was later refined by Lock and psychologist Daniel Le Grange, of UC San Francisco, who trained at Maudsley.

FBT asks parents to set aside many of their familys day-to-day activitiesscaling back school, work, hobbiesto sit with their children, requiring them to eat. Faced with food as a form of medicine, and with their world having contracted, many young people do start to eat again despite the fear and anxiety it causes them. Researchers are working to understand how FBT is intertwined with the biology of the illness, but for about half who try FBT in adolescenceand perhaps 70% who try it early in the diseasethe treatment is effective.

But many families arent told about that therapeutic strategy, even though decades have passed since it first showed success in a randomized trial, in 1987. Practitioners may not be familiar with FBT, Timko says, they may believe the family played a role in anorexias onset, or they may feel that adolescents must want to get better before starting FBTa view she disputes.

Laura Collins Lyster-Mensh experienced the regimen up close after her daughter Olympia, then 14, stopped eating one day in 2002. Lyster-Mensh says a succession of therapists urged her and her husband to stand back and let Olympia eat when she was ready. Meanwhile, her weight continued to spiral downward. We had been told she wouldnt recover, families were really at fault, to back off and let her do this on her own, Lyster-Mensh says. Then she learned about FBT from a newspaper article and raced to try it.

The first agonizing meals took hours, while Olympia mashed her food into a pulp or cried and raged at her parents. I know families whose kids have jumped out of moving cars to avoid a sandwich, says Lyster-Mensh, echoing comments of many clinicians who describe patients crushing fear of food. Olympia ultimately recovered, although not without challenges that included a relapse during college.

The young patients treated with FBT who do start to eat again do well on the one measure that predicts longer-term prognosis: early weight gain. In 2019, a study in theEuropean Eating Disorders Reviewled by Le Grange confirmed earlier research showing thatgaining about 2.3 kilograms in the first month of treatment is a predictor of health1 year later. Girls with anorexia who boosted their calorie intake and gained weight experienced increases in estrogen levels (which plummet in starvation), reduced stress, and improved ability to navigate different situations, a psychological trait called flexibility.

Researchers are exploring ways to build on and improve FBTor find new strategies to help patients in whom it has failed. Some clinical trials are testing whether certain talk therapies, such as cognitive behavioural therapy to help patients reframe their thinking, can helpfor example, by reducing anxiety or other impediments to eating.

New biological models of anorexia hint at other kinds of interventions. An 18-person study at Johns Hopkins University is offering the psychedelic drug psilocybin to patients. Early data suggest it holds promise in helping smokers quit and combating alcoholismand many researchers believe that in certain ways, anorexia shares some features with addiction. Park is leading a seven-person study of deep-brain stimulation in people with severe enduring anorexia, some of whom also have OCD.

Theres a certain neural network thats well characterized in OCD, she says, and disrupting the signaling in that network with deep-brain stimulation can help those patients. Because OCD and anorexia have shared features and some genetic links, shes interested in whether disrupting the same neural network might also help people with the eating disorder.

Still, studies remain sparse, Lock says. With limited funding, theres little chance of attracting new scientists to a small field. As researchers, you dont want to go to the pot thats empty, he says. Why arent we investing more? Its especially frustrating because, Lock points out, many patients with anorexia successfully heal and enjoy a bright future. What [other] illness in psychiatry can you say you cure? he asks.

For families, regardless of whether a patient recovers, the shame can persistand with it hesitation to speak up and lobby for funding. Lyster-Mensh is an exception. After her familys experience, she began to voice support for evidence-based treatmentfirst in a memoir,Eating with Your Anorexic, which she wrote under the name Laura Collins, and then throughFEAST, a message board turned advocacy group.

Its still a pretty small group, Lyster-Mensh says, of those willing to speak openly. Most families are so burned out, crushed, guilty, that they dont want to come forward, she says. There are still these myths out therethat these are chosen illnesses and parents somehow failed to prevent, or caused, or exacerbated the problem. Still, she hopes that as researchers doggedly track the diseases biological roots in genes and the brain, those enduring myths will fade.

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Rethinking anorexia: Biology may be more important than culture, new studies reveal - Science Magazine

Newswise MORGANTOWN, W.Va. Engineers in the Benjamin M. Statler College of Engineering and Mineral Resources at West Virginia University are using their expertise and equipment in a campus-wide effort to create personal protective equipment to keep up with the needs of health care providers in the fight against the COVID-19 pandemic.

Josh Bintrim and Kelsey Crawford, both Statler College graduates and Innovation Hub shop managers, have worked in collaboration with Hub Director Gene Cilento, Assistant Director Kolin Brownand health care professionals at WVU Health Sciences Center to design surgical mask extenders, face shields and intubation boxes for use in medical facilities.

Since initial production began two weeks ago, the Innovation Hub, a new prototyping center in development in the Statler College, has gone through multiple design iterations of products with input from physicians on the front lines of the pandemic.

The team has distributed more than 3,000 surgical mask extenders to local medical facilities, with calls coming in from California to Massachusetts, and even Ireland, requesting supplies and templates to create the mask extenders.

Now that medical professionals are required to wear surgical masks throughout their entire shift, there have been numerous reports of the masks causing irritation to the skin behind the ears. The mask extenders created in the Innovation Hub reduce the pressure behind the ears, affording the user an increased measure of comfort.

As long as supplies last, Bintrim and Crawford can use a laser cutter to create 300 extenders every hour.

Sourcing materials has been a big challenge, Crawford said. The response from the maker community has been great, but it has led to a shortage on clear, thin plastics. We have reached out to various companies and are adjusting previous designs to fit the materials that are available.

To maintain production of the face shields, the team is in need of 4 feet by 8 feet sheets of 0.03, 0.04 and .125 inch polycarbonate and 0.5 inch spools of elastic fabric, at least 6 inches long.

The team hopes to have an additional 3,000 surgical mask extenders, approximately 2,000 face shields and 40 intubation boxes completed and distributed to WVU Health Sciences Center and J.W. Ruby Memorial Hospital by the end of the week.

Parsing through all of the ideas and narrowing our focus on what we could do the fastest was a big challenge, Bintrim said. We went from 3D printing a face shield visor in five hours to completely redesigning the entire system to make an entire face shield in three minutes.

The Innovation Hub has made the directions for creating the face shields publicly available. The downloadable(231KB .zip) fileincludesface shield, visor and visor insert templates. See assembly video and materials required at bottom of article.

While the facility is not a manufacturing center, the team hopes that the templates will be used by companies who have the capacity to undergo mass distribution.

Obviously we wish that we could do everything, but we only have limited equipment and man hours, Bintrim said. I have always said that we are the college of engineering and that we should be the engineers for WVU. We now have a major collaboration between ourselves, HSC, Davis College and Eberly College and it allows us to do and be just that.

Now that the mask extenders and face shields have been in use for several days, Bintrim and Crawford explained that the feedback from health care workers has been very positive.

Everyone has been extremely grateful for the efforts that everyone is doing at WVU, Crawford said. We have had nurses and doctors almost in tears as they thank us.

The responses have been overwhelmingly positive, and people are incredibly thankful, Bintrim said. The hardest part is trying to tell everyone that we are the ones that are thankful for what they do and the risks they take every day by just going to work. We are just trying our best to support them in the fight.

To make donations of materials, questions regarding templates or distribution, contact Gene Cilento atGene.Cilento@mail.wvu.edu or by phone at 304-293-4088.

Downloadable templates, required materials and assembly video:

-WVU-

om/04/09/20

Call 1-855-WVU-NEWS for the latest West Virginia University news and information from WVUToday.

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West Virginia University partnerships help WVU Medicine community and beyond amidst personal protective equipment shortage - Newswise