Misfolded proteins (orange) in the endoplasmic reticulum may play a role in Wolfram syndromes many symptoms.

By Mitch LeslieFeb. 11, 2021 , 2:00 PM

Maureen Marshall-Doss says the first sign that her vision was deteriorating came when she misidentified the color of a dress. At a backyard get-together about 20 years ago, the Indianapolis resident pointed out an attractive yellow dress another woman was wearing. You see that as yellow? Shes wearing a pink dress, Marshall-Doss recalls her husband responding.

Today, Marshall-Doss is virtually blind. With help from custom made eyeglasses that magnify objects 500 times, I can see shapes, she says. But she can no longer drive and had to quit the job she loved as a school librarian. Along with her dimming vision, she has type 1 diabetes and has lost her sense of taste and smell.

Marshall-Doss is one of 15,000 to 30,000 people around the world with Wolfram syndrome, a genetic disease. For decades, the condition remained enigmatic, untreatable, and fatal. But in the past few years, insights into its mechanism have begun to pay off, leading to the first clinical trials of drugs that might slow the illness and sparking hopes that gene therapy and the CRISPR DNA-editing tool might rectify the underlying genetic flaws. Here is a rare disease that the basic science is telling us how to treat, says physiologist Barbara Ehrlich of the Yale School of Medicine.

The research could also aid more than the relatively few patients with Wolfram syndrome. Driving the diseases many symptoms is a malfunction of the endoplasmic reticulum (ER), the multichambered organelle that serves as a finishing school for many cellular proteins. Known as ER stress, the same problem helps propel far more common illnesses, including type 2 diabetes, amyotrophic lateral sclerosis (ALS), Parkinsons disease, and Alzheimers disease. Wolfram syndrome is the prototype of an endoplasmic reticulum disorder, says medical geneticist Fumihiko Fumi Urano of Washington University School of Medicine in St. Louis. Because Wolfram syndrome is simpler, says Scott Oakes, a cell biologist and pathologist at the University of Chicago, researchers think it could illuminate the mechanisms of other ER-disrupting diseases, which affect hundreds of millions of people worldwide.

In the late 1930s,four children with diabetes were going blind, and doctors were stumped. Like many other people in the United States struggling through the Great Depression, the siblings ate a paltry diet, subsisting on potatoes, bread, oatmeal, and a little milk. But after examining three of the children, Donald Wolfram, a physician at the Mayo Clinic in Rochester, Minnesota, and an ophthalmologist colleague ruled out malnutrition as the cause of their puzzling condition. Lead poisoning and syphilisthough common enoughwerent to blame, either. When Wolfram and his partner wrote up the cases in 1938, they concluded that the symptoms could be manifestations of an hereditary or acquired cerebral lesion.

The physicians were right that the syndrome eventually named for Wolfram is hereditary. Recessive mutations in the gene for a protein called wolframin are responsible for most cases, with glitches in a second gene causing most of the rest. However, the pair was wrong to think the defect lies only in the brain. Instead, the symptoms stem from widespread cell death. Its definitely a disease that affects the whole body, Marshall-Doss says.

The first sign of the illness, appearing when patients are children, is usually diabetes mellitus, or faulty sugar metabolism, sparked by the demise of insulin-secreting beta cells in the pancreas. Most patients also develop the unrelated condition diabetes insipidus, in which the pituitary gland doesnt dole out enough of a hormone that helps control the bodys fluid balance, causing the kidneys to produce huge amounts of urine.

Mutations in the gene for wolframin disrupt the endoplasmic reticulum and lead to cell death throughout the body, causing a range of symptoms.

V. Altounian/Science

Ellie White, 19, of Centennial, Colorado, who was diagnosed with Wolfram syndrome 12 years ago, says she hasnt had a full night of sleep since she was 3 years old. She gets up again and again to use the bathroom and monitor her blood sugar.

Yet she and other patients say that as disruptive as those problems are, they are not the diseases most dismaying consequence. The biggest symptom of Wolfram syndrome that affects me the most is my vision, White says. Because neurons in the optic nerve perish, patients usually go blind within 10 years of their first visual symptoms.

Other neurons die as well. As the disease progresses, brain cells expire, and walking, breathing, and swallowing become difficult. Most people with Wolfram syndrome die before age 40, often because they can no longer breathe. At 57, Marshall-Doss is one of the oldest patients; one of her mutated genes may yield a partly functional version of wolframin, triggering a milder form of the disease, Urano says.

Two advanceshave made it possible to begin to tackle those symptoms. The first was Uranos discovery nearly 20 years ago that linked Wolfram syndrome to ER stress. The ER is where about one-third of a cells newly made proteins fold into the correct shapes and undergo fine-tuning. Cells can develop ER stress whenever they are under duress, such as when they dont have enough oxygen or when misfolded proteins begin to pile up inside the organelle.

In test tube experiments, Urano and his colleagues were measuring the activity of genes to pinpoint which ones help alleviate ER stress. One gene that popped up encodes wolframin, which scientists had shown in 1998 was mutated in patients with Wolfram syndrome. Following up on that finding, Urano and his team determined that wolframin takes part in whats known as the unfolded protein response, which is a mechanism for coping with ER stress in which cells take steps including dialing back protein production.

Scientists think wolframin plays a key role in the unfolded protein response, though they havent nailed down exactly how. When wolframin is impaired, cells become vulnerable to ER stress. And if they cant relieve that stress, they often self-destruct, which could explain why so many neurons and beta cells die in the disease.

Defective wolframin may harm cells in other ways. The ER tends the cells supply of calcium, continually releasing and absorbing the ion to control the amount in the cytoplasm. Changes in calcium levels promote certain cellular activities, including the contraction of heart muscle cells and the release of neurotransmitters by neurons. And wolframin affects calcium regulation.

Beta cells genetically engineered to lack functional wolframin brim with calcium, Ehrlich and colleagues reported in July 2020 in theProceedings of the National Academy of Sciences. When exposed to lots of sugar, the altered cells release less insulin and are more likely to die than healthy beta cells, the team found. The cells share that vulnerability with beta cells from patients with Wolfram syndrome. We think that excess calcium is leading to excess cell death, Ehrlich says.

ER malfunctions could hamstring other organelles as well. The ER donates calcium to the mitochondria, the cells power plants, helping them generate energy. In 2018, a team led by molecular biologist Ccile Delettre and molecular and cellular biologist Benjamin Delprat, both of the French biomedical research agency INSERM, discovered that in cells from patients with Wolfram syndrome, mitochondria receive less calcium from the ER and produce less energy. Those underpowered mitochondria could spur the death of optic nerve cells, the researchers speculate.

Fumihiko Urano holds dantrolene, a muscle relaxant drug he helped test as a treatment for Wolfram syndrome.

The link between ER stress and Wolfram syndrome has been crucial for identifying potential treatments because otherwise we would have nothing to target, Urano says. But a second development was also key, he says: the advocacy and support of patient organizations, such as the Snow Foundation and the Ellie White Foundation, headed by its namesakes mother. The foundations have stepped up with money for lab research and clinical trials when other sources, including government agencies, didnt come through.

Scientists, patients, and their advocates say Urano also deserves much of the credit. Besides treating patients, he heads the international registry of cases and has taken the lead in organizing clinical trials, screening compounds for possible use as treatments, and devising potential therapies. Fumi is clearly the driving force, says Stephanie Snow Gebel, co-founder of the Snow Foundation, who about 10 years ago helped persuade him to forgo a plum job as department chair at a Japanese university and take over the Wolfram program at Washington University.

Patients could soonstart to reap the benefits. In 2016, Urano and colleagues started the worlds first clinical trial for the disease: a phase 1/2 study of dantrolene, an approved muscle relaxant. The molecule was a top performer when they screened 73 potential treatments for their ability to save cells with terminal ER stress. Dantrolene didnt improve vision in the 22 participants, including White, the scientists reported in an October 2020 preprint. But in some patients, beta cells appeared to be working better and releasing more insulin. The drug is safe, but Urano says it will need to be chemically tweaked to target its effects before future trials are warranted.

Researchers are pursuing other possible treatments targeting ER stress or calcium levels. In 2018, U.K. scientists launched a trial that will include 70 patients to evaluate sodium valproate, a therapy for bipolar disorder and epilepsy that, in the lab, prevents cells with faulty wolframin from dying. Last year, another compound that emerged from Uranos screens, the diabetes drug liraglutide, entered a clinical trial. Also last year, an experimental drug developed by Amylyx Pharmaceuticals for Alzheimers disease and ALS received orphan drug designation from the U.S. Food and Drug Administration for Wolfram syndrome because it curbs ER stress. That designation offers tax breaks and other incentives, and it will get trials started sooner, Urano says.

Ehrlich and her team have a candidate of their own that they have begun to test in rodents: the drug ibudilast, which is approved in Japan to treat asthma. The researchers found it reduces calcium levels in beta cells lacking wolframin and boosts their survival and insulin output. New screening projects may reveal still more candidates.

But Urano knows that even if a treatment receives approval, it would be only a Band-Aid for Wolfram syndrome. Hoping to develop a genetic cure, he and colleagues are introducing replacement genes into cells from patients and from mice engineered to replicate the disease. The researchers are endowing the cells with healthy copies of the gene for wolframin or the gene for a protein that reduces ER stress to determine whether they restore cellular function and reduce cell death. At INSERM, Delettre and colleagues are also evaluating whether directing a working gene into optic nerve cells can curtail vision loss in mice with faulty wolframin. The scientists are still gathering data, but early results suggest the treatment can halt the deterioration.

Urano and his collaborators have also turned to the genome editor CRISPR, deploying it to correct the gene defect in patients stem cells and then growing them into beta cells. When the researchers transplanted the revamped cells into mice with diabetes, the animals blood sugar returned to healthy levels, the team reported in April 2020 inScience Translational Medicine.

Stem cell biologist Catherine Verfaillie of KU Leuven is collaborating on the CRISPR research. But she notes that because the faulty wolframin gene affects so many tissues, researchers will have to figure out how to deliver the CRISPR components to most cells in large organs such as the brain and livera prospect she calls pretty daunting. Urano agrees, predicting that CRISPR-based Wolfram therapies might take 10 to 20 years to develop. The alternative approach, gene therapy, could reach clinical trials more quickly, in 3 to 10 years, he says, because researchers have more experience with gene therapy and have created several treatments that have already been approved for other illnesses.

Because it stems from a single genetic glitch, Wolfram syndrome could also help scientists tease out the role of the ER in more complex diseases, including neurological conditions, type 2 diabetes, and cancer. The ER also falters in those diseases, causing cells to die, but the mechanism is harder to discern because they stem from myriad genetic and environmental factors. In Alzheimers disease, for instance, neurons develop ER stress as misfolded proteins accumulate inside and outside the cells.

Besides deepening researchers understanding of other conditions, the research on Wolfram syndrome might even deliver candidate treatments. Everyone would be very excited if we can make advances in targeting ER stress in Wolfram syndrome, Oakes says. It would open up the whole field to doing this in other degenerative diseases.

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The race to treat a rare, fatal syndrome may help others with common disorders like diabetes - Science Magazine

SALT LAKE CITY, Feb. 11, 2021 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, announced today that it will participate at multiple upcoming health and technology conferences, sharing insights on how the company is intensifying its focus on serving patients and healthcare providers in Womens Health, Oncology and Mental Health.

Paul J. Diaz, president and CEO at Myriad Genetics, and R. Bryan Riggsbee, CFO, will participate in a fireside chat at the BTIG Virtual MedTech, Digital Health, Life Science & Diagnostic Tools Conference on February 19 at 10:30 a.m. EST.

On February 24, 2021, Mr. Riggsbee will participate in a fireside chat at the Leerink Global Healthcare Conference at 5:00 p.m. EST.

On March 2, 2021, Mr. Diaz will participate in a fireside chat at the Cowen Annual Healthcare Conference at 9:50 a.m. EST.

The presentations will be available through a live audio webcast link in the investor information section of Myriads website at http://www.myriad.com.

About Myriad GeneticsMyriad Genetics, Inc. is a leading genetic testing and precision medicine company dedicated to improving health and transforming patient lives worldwide. Myriad discovers and commercializes genetic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across medical specialties where critical genetic insights can significantly improve patient care and lower healthcare costs. For more information, visit the Company's website: http://www.myriad.com.

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

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Myriad Genetics to Participate in Multiple Upcoming Health and Technology Conferences - GlobeNewswire

PROVIDENCE, R.I.[Brown University] New research provides insights into the treatment of Christianson syndrome (CS), an X-linked genetic disease characterized by reduced brain growth after birth, intellectual disability, epilepsy and difficulties with balance and speech.

One of the major challenges in developing treatments for human brain disorders, like CS, is developing an experimental system for testing potential therapeutics on human neurons, said study senior author Dr. Eric Morrow, an associate professor of molecular biology, neuroscience and psychiatry at Brown University. In recent years, advanced stem cell therapies that use tissues from patients have provided powerful new approaches for engineering human neurons from the patients themselves, who may undergo the treatment in the future.

For the study, published in Science Translational Medicine on Feb. 10, 2021, Morrow and his colleagues obtained blood samples from five CS patients and the patients unaffected brothers. They then reprogrammed these blood cells into stem cells, and these stem cells were converted into neurons in a petri dish. As a result, they obtained neurons that were representative of those from CS patients, and they used these neurons to test treatments.

Morrow who directs the Center for Translational Neuroscience at the Carney Institute for Brain Science and the Brown Institute for Translational Science said the team also used a new gene-editing approach that employs CRISPR-Cas9 technologies to correct patient mutations back to a healthy gene sequence.

CS is caused by a mutation in a gene encoding for NHE6, a protein that helps regulate acid levels within cell structures called endosomes. Past research suggests that the loss of NHE6 causes endosomes to become overly acidic, which disrupts the abilities of developing neurons to branch out and form connections in the growing brain.

Loss of this important protein can arise from a variety of gene mutations in patients. The majority of CS mutations are called nonsense mutations, which prevent NHE6 from being produced at all; four of the five CS patients involved in this study exhibited this class of mutation. However, some CS patients exhibit missense mutations. Individuals with missense mutations still have some NHE6, but it is produced in smaller amounts, and the protein fails to function as it should.

The research team tested two main forms of treatment on the stem-cell-derived neurons: first, gene transfer, which involves adding a healthy NHE6 gene into the cell; and second, administration of trophic factors, which are substances that promote neuron growth and encourage neurons to develop connections with other neurons. The researchers found that the neurons response to treatment depended on the class of mutation present.

The gene transfer studies, which may represent the first steps toward developing gene therapy, were successful in neurons with nonsense mutations. After the researchers inserted a functional NHE6 gene into nonsense-mutation CS neurons, the neurons branched out properly. In neurons with missense mutations, however, gene transfer failed completely. Further tests suggested that the abnormal NHE6 produced as a result of missense mutations may interfere with normal NHE6, thereby rendering gene transfer therapy ineffective in patient cells with these mutations.

In contrast, administration of trophic factors, such as brain-derived neurotrophic factor (BDNF) and insulin-like growth factor-1 (IGF-1), successfully promoted proper branching in all the CS neurons studied, regardless of mutation type.

While these initial results are encouraging, Morrow hopes that future studies will examine these treatments in animal models.

Our results provide an initial proof-of-concept for these treatment strategies, indicating that they should be studied further, he said. However, we may ultimately need to pay close attention to the class of mutation that a patient has when we choose a specific treatment.

In addition to Morrow, the research team included scientists from Brown University, the University of South Carolina and the Icahn School of Medicine at Mount Sinai. The study was supported by multiple grants from the National Institutes of Health as well as a number of awards from foundations and academic institutions.

This news story was authored by contributing science writerKerry Benson.

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Neurons from patient blood cells enable researchers to test treatments for genetic brain disease - Brown University

How often a person takes daytime naps, if at all, is partly regulated by their genes, according to new research led by investigators at Harvard-affiliated Massachusetts General Hospital (MGH) and published inNature Communications.

In this study, the largest of its kind ever conducted, the MGH team collaborated with colleagues at the University of Murcia in Spain and several other institutions to identify dozens of gene regions that govern the tendency to take naps during the day. They also uncovered preliminary evidence linking napping habits to cardiometabolic health.

Napping is somewhat controversial, says Hassan Saeed Dashti of the MGH Center for Genomic Medicine, co-lead author of the report with Iyas Daghlas, a medical student at Harvard Medical School (HMS). Dashti notes that some countries where daytime naps have long been part of the culture (such as Spain) now discourage the habit. Meanwhile, some companies in the United States now promote napping as a way to boost productivity. It was important to try to disentangle the biological pathways that contribute to why we nap, says Dashti.

Previously, co-senior author Richa Saxena, principal investigator at the Saxena Lab at MGH, and her colleagues used massive databases of genetic and lifestyle information to study other aspects of sleep. Notably, the team has identified genes associated with sleep duration, insomnia, and the tendency to be an early riser or night owl. To gain a better understanding of the genetics of napping, Saxenas team and co-senior author Marta Garaulet of the department of physiology at the University of Murcia, performed a genome-wide association study (GWAS), which involves rapid scanning of complete sets of DNA, or genomes, of a large number of people. The goal of a GWAS is to identify genetic variations that are associated with a specific disease or, in this case, habit.

For this study, the MGH researchers and their colleagues used data from the UK Biobank, which includes genetic information from 452,633 people. All participants were asked whether they nap during the day never/rarely, sometimes or usually. The GWAS identified 123 regions in the human genome that are associated with daytime napping. A subset of participants wore activity monitors called accelerometers, which provide data about daytime sedentary behavior, which can be an indicator of napping. This objective data indicated that the self-reports about napping were accurate. That gave an extra layer of confidence that what we found is real and not an artifact, says Dashti.

Several other features of the study bolster its results. For example, the researchers independently replicated their findings in an analysis of the genomes of 541,333 people collected by 23andMe, the consumer genetic-testing company. Also, a significant number of the genes near or at regions identified by the GWAS are already known to play a role in sleep. One example isKSR2, a gene that the MGH team and collaborators had previously found plays a role in sleep regulation.

Digging deeper into the data, the team identified at least three potential mechanisms that promote napping:

This tells us that daytime napping is biologically driven and not just an environmental or behavioral choice, says Dashti.

Some of these subtypes were linked to cardiometabolic health concerns, such as large waist circumference and elevated blood pressure, though more research on those associations is needed.

Future work may help to develop personalized recommendations for siesta, says Garaulet.

Furthermore, several gene variants linked to napping were already associated with signaling by a neuropeptide called orexin, which plays a role in wakefulness. This pathway is known to be involved in rare sleep disorders like narcolepsy, but our findings show that smaller perturbations in the pathway can explain why some people nap more than others, says Daghlas.

Saxena is the Phyllis and Jerome Lyle Rappaport MGH Research Scholar at the Center for Genomic Medicine and an associate professor of anesthesia at HMS.

The work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Heart, Lung, and Blood Institute, MGH Research Scholar Fund, Spanish Government of Investigation, Development and Innovation, the Autonomous Community of the Region of Murcia through the Seneca Foundation, Academy of Finland, Instrumentarium Science Foundation, Yrj Jahnsson Foundation, and Medical Research Council.

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The science behind those afternoon naps Harvard Gazette - Harvard Gazette

BOSTON--(BUSINESS WIRE)--Ensoma, a company expanding the curative power of genomic medicine by pioneering a next-generation in vivo approach, today launched with a $70 million Series A financing led by co-founder and seed investor 5AM Ventures, with participation from F-Prime Capital, Takeda Ventures, Viking Global Investors, Cormorant Asset Management, RIT Capital Partners, Symbiosis II, LLC, and Alexandria Venture Investments. In addition to an equity investment of $10 million in the Series A financing, Takeda Pharmaceutical Company Limited (Takeda) and Ensoma have entered into a strategic collaboration with the potential for upfront and preclinical research payments totaling $100 million as part of a strategic collaboration worth up to $1.25 billion, announced in a separate press release this morning.

The foundation of the companys platform its Engenious vectors is based on over two decades of academic and clinical research generated by scientific co-founders and renowned experts, Hans-Peter Kiem, M.D., Ph.D., of Fred Hutchinson Cancer Research Center, and Andr Lieber, M.D., Ph.D., of University of Washington School of Medicine. The company will be led by biotechnology industry veterans with demonstrated track records in innovative therapeutic modalities, including gene therapy and editing, across an array of disease areas, including rare disease, hematology and oncology.

Ensomas Engenious vectors are designed to deliver a diverse range of genome modification technologies including those that require a high level of packaging capacity directly to hematopoietic stem cells (HSCs) or the various cell types that arise from these cells, such as T cells, B cells and myeloid cells. The companys vectors are optimized to work without the need for stem cell collection or prior myeloablative conditioning (e.g., chemotherapy). As a result, Ensomas therapies will be designed to be delivered via single injection in diverse environments, including outpatient and areas where access to sophisticated healthcare systems may be limited.

With the launch of Ensoma, we aspire to bring innovative new treatments to patients in a way that is accessible for all, said Paula Soteropoulos, executive chairman of Ensoma. Because our in vivo therapies do not require prior conditioning or stem cell donors, we hope to deliver them as off-the-shelf treatments to address diseases both rare and common dramatically simplifying the logistics of scaling production and reducing patient and healthcare-system burden. Every person, no matter where they are in the world, should have access to the innovative technologies that are changing the way we treat disease.

Engenious Vectors

Ensomas Engenious vectors are specially engineered adenovirus vectors devoid of any viral genome and minimal pre-existing immunity, thus minimizing the chance of an immune response and freeing up ample storage space up to 35 kilobases (kb) of DNA packaging capacity to deliver a diverse range of genome modification technologies. Also known as therapeutic cargo, these technologies may include, separately and in combination, the following:

These approaches enable Engenious vectors to engineer various erythroid, lymphoid (e.g., T cells, B cells) and myeloid (e.g., macrophages, microglia) cell types, with great precision and vast therapeutic potential. Addressable indications range from rare monogenic diseases to broader diseases such as oncology, autoimmunity and infectious diseases via precision, off-the-shelf engineering of the immune system.

Given the highly specific nature of these technologies, Ensomas Engenious vectors enable preferential targeting of HSCs inside the body. Additionally, Ensomas founders have developed an in vivo selection system that can increase the population of genetically modified HSCs, if needed. This proprietary approach enables precise titration to lasting therapeutic levels without the need to re-dose patients, bypassing the immunogenic challenges associated with re-dosing for some other gene therapy modalities.

Ensomas Engenious platform has been extensively validated in numerous preclinical models with a range of genome editing technologies, demonstrating robust genetic modification of bone marrow HSCs and stable long-term expression of therapeutic proteins in small and large preclinical models.

There have been tremendous advancements in technologies to precisely target, genetically edit and modify human disease. However, many of these tools pose delivery challenges; some lack the ability to reach the right cells within the body, while others lack the ability to broadly reach significant numbers of patients due to complex procedures and supply chain challenges, said Kush M. Parmar, M.D., Ph.D., founding chief executive officer of Ensoma. Ensomas scientific approach allows us to do what hasnt been done beforeto make the curative power of genomic medicine and stem cell technology portable so they may be administered in low-resource and outpatient settings for the very first time.

Leadership & Scientific Founders

Ensoma was founded by and incubated within the 4:59 Initiative, the company creation engine of 5AM Ventures. The companys scientific co-founders include Dr. Hans-Peter Kiem, an oncologist and world-renowned pioneer in gene-editing technologies, including stem cell and gene therapies, from Fred Hutch, who also serves as vice president of the American Society of Gene & Cell Therapy and chief scientific and clinical advisor for Ensoma; and Dr. Andr Lieber, an accomplished academic researcher and professor of medicine, Division of Medical Genetics, UW School of Medicine, who has studied the biological and translational aspects of human adenoviruses for more than two decades. Ensoma is based on an exclusively licensed portfolio of technologies developed by the Fred Hutch lab of Dr. Kiem and the University of Washington lab of Dr. Lieber that enable in vivo genome engineering and gene therapy advances of HSCs for therapeutic use in blood diseases.

Following more than 20 years of academic and clinical research, Ensoma has assembled an exceptional team to boldly forge a new era of genomic medicine in vivo, said Bihua Chen, founder and portfolio manager at Cormorant Asset Management. The company is moving swiftly to accelerate and broaden the therapeutic potential of its approach, and I am confident they have the right team and the right technology to potentially bring life-changing, curative therapies within reach for people all over the world.

Additional details surrounding company leadership, including its board of directors, are as follows:

Ensoma has also named its scientific advisory board, which may be viewed here.

About 5AM Ventures

Founded in 2002, 5AM actively invests in next-generation biotech companies. With approximately $1.5 billion raised since inception, 5AM has invested in 89 companies. For more information, please visit http://www.5amventures.com.

About the 4:59 Initiative

The 4:59 Initiative is the internal company creation engine at 5AM Ventures that helps discover, incubate, and fund breakthrough science. The 4:59 team provides hands-on scientific, strategic, and operational support, working closely with academics and entrepreneurs to advance breakthrough science and establish proof-of-concept data to enable a clear path to transformative therapies for patients.

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Ensoma Launches to Pioneer Next-Generation In Vivo Approach to Deliver First Off-the-shelf Genomic Medicines - Business Wire

With a Takeda collaboration already in its pocket, Ensoma announced a $70 million Series A round to help develop its platform of engineered gene therapy vectors for off-the-shelf in vivo therapeutics, starting in rare diseases.

The venture round was led by 5AM Ventures, which co-founded and seeded Ensoma. F-Prime Capital, Takeda Ventures, Viking Global Investors, Cormorant Asset Management, RIT Capital Partners, Symbiosis II, LLC and Alexandria Venture Investments also participated, with Takeda making a $10 million equity investment in the new company.

As part of the Takeda deal, Ensoma will do preclinical research for therapies in up to five rare disease indications, and both companies will work on Investigational New Drug (IND)-enabling studies. Takeda has an exclusive license for Ensomas vectors in the chosen indications. Upfront payments alone were not disclosed, but Ensoma could earn up to $100 million for its early-stage work and up to $1.25 billion overall in milestone payments.

Ensoma is developing helper-dependent adenoviral vectorsvectors with viral coding sequences removedthat would not be limited to ex vivo editing for autologous cell therapies or require myeloablative conditioning to prepare a patients immune system.

The technology is based on the work of scientific co-founders Hans-Peter Kiem and Andr Lieber. Kiem is director of the Stem Cell and Gene Therapy Program Clinical Research Division at Fred Hutchinson Cancer Research Center, and Lieber is a professor of medical genetics at the University of Washington School of Medicine.

In September, Liebers lab published preclinical findings that showed bi-modular helper-dependent adenoviral vectors could deliver a therapeutic gene therapy in vivo to hematopoietic stem cells (HSCs) in a mouse mode of sickle cell disease.

According to the company, its engineered vectors can be specifically targeted to deliver large payloads for a diverse array of genome-modifying technologies in vivo, not just to HSCs but also the cells those generate like T, B and myeloid cells. And because the vectors have been engineered to lack a viral genome, they are expected to have lower immunogenicity than lentiviral vectors typically used for in vivo genetic therapies, without the need for redosing.

The Ensoma platform offers distinct advantages over AAV and ex vivo lentiviral gene therapy approaches with the potential to overcome some of the challenges associated with first-generation technologies, said Takeda Rare Diseases Drug Discovery Unit Head Madhu Natarajan.

Takeda made similar forays in search of a post-adenoviral vector delivery approach last year. In June, it partnered with extracellular vesicles (EVs) company Carmine Therapeutics to develop and commercialize non-viral gene therapies for two rare diseases. Carmine is developing EVs derived from engineered O-type blood cells as vehicles for gene therapies. And last March, Takeda also partnered with EV company Evox Therapeutics for therapies in up to five rare disease indications.

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Ensoma Launches with $70 Million Series A and Takeda Licensing Deal - BioSpace

A scanning electron micrograph of an oral squamous cancer cell (white) being attacked by two cytotoxic T cells (red), part of a natural immune response. Image by NIH

For all their importance as a breakthrough treatment, the cancer immunotherapies known as checkpoint inhibitors still only benefit a small minority of patients, perhaps 15 percent across different types of cancer. Moreover, doctors cannot accurately predict which of their patients will respond.

A new study finds that inherited genetic variation plays a role in who is likely to benefit from checkpoint inhibitors, which release the immune systems brakes so it can attack cancer. The study also points to potential new targets that could help even more patients unleash their immune systems natural power to fight off malignant cells.

People who respond best to immunotherapy tend to have inflamed tumors that have been infiltrated by immune cells that are capable of killing both viruses and cancer. This inflammation is also driven by the immune signaling molecule interferon.

There are some factors that are already associated with how well the immune system responds to tumors, said Elad Ziv, MD, professor of medicine at UCSF and co-senior author of the paper, published Feb. 9, 2021, by an international team in Immunity. But whats been less studied is how well your genetic background predicts your immune systems response to the cancer. Thats what is being filled in by this work: How much is the immune response to cancer affected by your inherited genetic variation?

The study suggests that, for a range of important immune functions, as much as 20 percent of the variation in how different peoples immune systems are able to attack cancer is due to the kind of genes they were born with, which are known as germline genetic variations.

That is a significant effect, similar to the size of the genetic contribution to traits like high blood sugar levels or obesity.

Rather than testing selected genes, we analyzed all the genetic variants we could detect across the entire genome. Among all of them, the ones with the greatest effect on the immune systems response to the tumor were related to interferon signaling. Some of these variants are known to affect our response to viruses and our risk of autoimmune disorders, said Davide Bedognetti, MD, PhD, director of the Cancer Program at the Sidra Medicine Research Branch in Doha, Qatar, and co-senior author of the paper. As observed with other diseases, we demonstrated that specific genes can also predispose someone to have a more effective anti-cancer immunity.

The team identified variants in 22 regions in the genome, or in individual genes, with significant effects including one gene, IFIH1, that is already well known for the role its variants play in autoimmune diseases as varied as type 1 diabetes, psoriasis, vitiligo, systemic lupus erythematosus, ulcerative colitis and Crohns disease.

The IFIH1 variants act on cancer immunity in different ways. For instance, people with the variant that confers risk of type 1 diabetes had a more inflamed tumor, which suggests they would respond better to cancer immunotherapy. But the researchers saw the opposite effect for patients with the variant associated with Crohns, indicating they might not benefit.

Another gene, STING1, was already thought to play a role in how patients respond to immunotherapy, and drug companies are looking for ways to boost its effects. But the team discovered that some people carry a variant that makes them less likely to respond, which may require further stratification of patients to know who could benefit most from those efforts.

The study required a huge amount of data that could only be found in a dataset as large as The Cancer Genome Atlas (TCGA), and from which they analyzed the genes and immune responses of 9,000 patients with 30 different kinds of cancer.

All told, the scientific team, which includes members from the United States, Qatar, Canada, and Europe, examined nearly 11 million gene variants to see how they matched with 139 immune parameters measured in patient tumor samples.

But the 22 regions or genes identified in the new study are just the tip of the iceberg, the researchers said, and they suspect many more germline genes likely play a role in how the immune system responds to cancer.

The next step, Ziv said, is to use the data to formulate polygenic approaches taking a large number of genes into account to predict which cancer patients will benefit from current therapies, and developing new drugs for those who will not.

Its further off, he said, but its a big part of what we hope will come out of this work.

The co-first authors are Rosalyn Sayaman, PhD, at UCSF and City of Hope and Mohamad Saad, PhD, of Qatar Computing Research Institute at Hamad Bin Khalifa University in Doha, Qatar. See the paper online for additional author, funding and disclosure information.

The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.UCSF Health, which serves as UCSFs primary academic medical center, includes top-ranked specialty hospitals and other clinical programs, and has affiliations throughout the Bay Area.

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Response to Cancer Immunotherapy May Be Affected by Genes We Carry from Birth - UCSF News Services

If theres one thing Ive learned over the years as a health and wellness writer, its that information is power. The flip side of that is the fact that not having key information available to you can be deeply disempowering. Like millions of other Americans, Im adopted, which means I havent been able to find out a lot about important health information that most people have readily available to them: family health history and genetic health information.

Family health history is essentially just that: knowing the health histories of members of your biological family. This kind of information can help doctors pinpoint whether you are at risk for certain health conditions that can run in families or be determined by genetics. Family history is a strong clue for chronic disease risks you may face, such as heart disease, stroke, cancer, and diabetes, says Latha Palaniappan, MD, the scientific director of Genomics and Pharmacogenomics in Primary Care at Stanford Medicine. The Centers for Disease Control and Prevention (CDC) CDC recommends documenting as much as you can about your familys health history in order to share with your doctor, and ask for additional testing if youre concerned about your risk for a specific disease.

While Ive always valued a healthy lifestyleI try to eat well, sleep enough, exercise, and manage stress as much as possibleIve wondered recently if my inclination towards healthy living has been driven in part by fear, specifically the fear of what I dont know about my health and genetics. Since I dont know what could be in my genes, at least I do have some control over my lifestyle now, and that counts for a lot, right?

Thankfully, Dr. Palaniappan assures me that family history is not the end-all, be-all of what will happen with your health.Family history is probabilistic, not predictive, she says. (Basically, it can educate you about your odds of experiencing a certain health outcome, but not predict it outright.) But if you do have access to that information, use it, since family history provides important clues about your health risks, says Dr. Palaniappan.

So if you dont have access to this information, should you be worried? And what else can you do, besides actually going out to try to find your biological relatives information (which is a hugely personal choice, and not possible for some)? There are some other things you can do to help you gather more information about your health and feel more empowered about your future.

Honestly, I didnt think about my family health history too much until I started approaching 30. As the mystery surrounding family health information came up a bit more for me, I talked to my mom and my sister about my concerns surrounding what we dont know. When my mom got me a 23andMe DNA test (which start at $199 for the Health + Ancestry test) for Christmas one year, I was excitedand kind of anxiousto have the chance to take a deeper look into my health information.

23andMe is just one example of a direct-to-consumer (DTC) DNA test that can give you some more information about your health. According to the companys website, the health reports available with the test include genetic information that can clue you in to your genetic risk for conditions like type 2 diabetes, select variants of BRCA1/BRCA2 (the gene associated with breast, ovarian, and pancreatic cancer), celiac disease, uterine fibroids, and more. The brands test can tell you about your carrier status (meaning if you carry genes linked to an inherited disease that could affect your children) for some diseases like cystic fibrosis and sickle cell anemia.

However, these DTC tests dont often come with specific consultation to walk you through whats present in your genome and how that translates into actual risk. Thats why its important to work with a genetics expert or genetic counselor if you can, says Robert C. Green MD, a medical geneticist who leads the Preventative Genomics Clinic at the Harvard-affiliated Brigham and Womens Hospital, and is the director of the Genomes2People Research Program.You [can] have a geneticist or genetic counselor who basically talks to you about what [the test results] mean and what should you do about it. What should you worry about and what should you not worry about, says Dr. Green. For example, if you tested positive for the gene for a certain hereditary cancer, a genetic counselor can help you with the next steps, like if you should seek more testing or work with a specialist.

Dr. Green adds that DTC tests arent the most comprehensive testing option. Thats because most of them use whats called chip-based DNA technology, which essentially scan your genome for known common mutations or markers along your genome, he says. [This technology] can be very good for ancestry for [finding relatives] and for certain specific markers, such as the Ashkenazi Jewish BRCA1 mutation that 23andMe looks for. It does not look at every letter in your genes, and its not typically set up to find rare or novel mutations that can affect your health. (Theyre not always super accurate, eithera 2019 study found that these chips have a very high false-positive rate for rare genetic mutations.) For health reasons sequencingwhich looks at every letter in a segment of your genome or across the whole genomeis more expensive, but much, much more comprehensive, he says.

DNA testing is definitely not cheap (it can run anywhere from $200 up to $2,000 for the more in-depth testing, and isnt always covered by insurance) and its certainly not the only way to find out more information about your health.

If you dont know much about your family health history, Dr. Palaniappan encourages paying attention to key health markers including blood pressure, cholesterol, glucose, and heart rate, and getting those checked regularly. These measurable risk factors can be effectively treated to reduce your risk of heart disease, stroke and diabetes, says Dr. Palaniappan. Everyone can reduce the risk of disease by eating a healthy diet, getting enough exercise, and not smoking. Cancer screening tests such as mammograms and colorectal cancer screening can detect precancer and treatable cancers early, she says.

While getting the DNA test felt like a great first step to knowing more about my health, its also good to know that the everyday things that I sometimes dont even think about (like walking my dog) might have a bigger impact on my health than I thought before.What you do each and every daywhat you eat, how much you exercise, and your other health behaviors, can ultimately affect your risk of developing disease, says Dr. Palaniappan. If anything, Ive learned that not knowing your family health history doesnt have to be a huge blank spot, but if I ever do want to know more, there are optionswhich is empowering for sure.

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Im 28 and I Dont Know My Family HistoryHeres How That Affects My Health - Well+Good

Recently demonstrated single-dose intravenous administration of a PATrOL-enabled compound resolves the causal genetic defect in myotonic dystrophy type 1 (DM1) in transgenic animals; Company on course to move one program into clinical development in CY2022

Plans to host an R&D day in the first half of CY2021 to provide updates on platform innovations, the DM1 and Huntington's disease (HD) programs and pipeline expansion in high value indications

Expects to complete consolidation of intellectual property in the space through acquisition of gene modulating technology from Vera Therapeutics in Q1 CY2021

PITTSBURGH, Feb. 11, 2021 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq: NBSE) ("NeuBase" or the "Company"), a biotechnology company accelerating the genetic revolution using a new class of synthetic medicines, today reported its financial results for the three-month period ended December 31, 2020.

"In 2020 we validated that our PATrOL platform technology can deliver compounds that are broadly biodistributed, mutant allele-specific and well tolerated, including in non-human primates (NHPs). Thereafter we finalized screening compound libraries and moved into in vivo efficacy and tolerability studies that demonstrated that administration of a PATrOL-enabled compound resolves the causal genetic insult in an established transgenic animal model of myotonic dystrophy type 1 (DM1), a severe genetic disease with no effective therapies. This momentum is being carried forward into 2021 as we set the stage to enter the clinic in CY2022," said Dietrich A. Stephan, Ph.D., chief executive officer of NeuBase. "Predicated on our progress, we recently announced an agreement to acquire additional gene modulating technology to consolidate the intellectual property to protect and enhance value creation with this unique therapeutic modality."

"We look forward to providing more data and insights during an investor R&D day in the first half of CY2021, including updates on platform innovations, continued progress in Huntington's disease (HD) and DM1 and new pipeline programs. This event will provide an opportunity for us to introduce the expanded team, including Dr. Curt Bradshaw, Ph.D. chief scientific officer, who has overseen several development programs into the clinic and complements a world-class team of technical experts and drug developers."

First Quarter of Fiscal Year 2021 and Recent Operating Highlights

Financial Results for the Fiscal Quarter Ended December 31, 2020

About NeuBase TherapeuticsNeuBase is accelerating the genetic revolution using a new class of synthetic medicines which have been shown to be able to increase, decrease and change gene function, as appropriate, to resolve causal genetic defects in living systems. NeuBase's designer PATrOL therapies are centered around its proprietary drug scaffold to address genetic diseases at the source by combining the highly targeted approach of traditional genetic therapies with the broad organ distribution capabilities of small molecules. With an initial focus on silencing disease-causing mutations in debilitating neurological, neuromuscular and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions. To learn more, visit http://www.neubasetherapeutics.com.

Use of Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods. These forward-looking statements include, among others, those related to the potential significance and implications of the Company's positive in vitro and in vivo preclinical data for its PATrOL-enabled anti-gene therapies for the treatment of myotonic dystrophy type 1 (DM1), the plan to provide updates on the Company's development pipeline, including the myotonic dystrophy type 1 (DM1) and Huntington's disease (HD) programs, at an R&D day in the first half of CY2021 and the Company's anticipated capital requirements over approximately the next twelve months. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the risks that prior data will not be replicated in future studies; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com OP: (617) 430-7576

NeuBase Media Contact:Cait Williamson, Ph.D.LifeSci Communicationscait@lifescicomms.com OP: (646) 751-4366

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NeuBase Therapeutics Reports Financial Results for the First Quarter of Fiscal Year 2021 - GlobeNewswire

For baby Teera Kamat, who has been on the earth for a mere six months, every day has been a struggle for existence and a grim reminder to her parents about the fragile little being that needed a miracle to be saved. Mumbai-born Teera is suffering from Spinal Muscular Atrophy, a very rare medical condition that often does not let children live beyond 5 months of age and her condition requires a lot of money for the treatment.

On Wednesday, Prime Minister Narendra Modi, in a humanitarian move, decided to waive off Rs 6 crore as a GST amount against Rs 16 crore of imported medicines that are required to treat Teera. Baby Teera's parents Priyanka and Mihir Kamat have raised Rs 16 crore through crowdfunding for their daughter who needs a surgery to be cured. It also includes the cost of the medicine Zolgensma which has to be imported from the US. The tax exemption for baby's treatment amounts to at least Rs 6.5 crore and it includes 23 percent import duty and 12 percent Goods Services Tax.

The infant's parents had earlier appealed to PM Modi in October last year about Teeras medical condition and in January this year. The Leader of Opposition Devendra Fadnavis also wrote to the Prime Minister and Finance Minister Nirmala Sitaraman reiterating the request to exempt taxes on the medicine import.

It is a type of genetic disorder and a motor neuron disease that results in a person not having any control over movement of their muscles due because of the lack of nerve cells, in their spinal cord and/or brain stem.

Spinal muscular atrophy (SMA) results in muscle wasting and weakness. For someone suffering from SMA, it is very difficult to stand, walk and control their movements. Some intense forms of the SMA can also result in inability to breathe and swallow.

SMA can either occur at birth or even appear at stages of life and they can affect one's life expectancy depending upon the seriousness and the type of the SMA.

So far, there has been no cure of SMA, but certain medicines do help, such as nusinersen (Spinraza) and onasemnogene abeparvovec-xioi (Zolgensma), that help slow the disease's progress.

The types of SMA depend on when they start showing up in a patient and how the symptoms vary in them. There are basically four kinds of SMA, as National Institute of Neurological Disorders and Stroke list, which affects symptoms and life expectancy.

The first type of SMA, or Werdnig-Hoffmann disease appears before the infant is even 6 months of age. The child might be born with difficulty in breathing and the serious condition can turn fatal if there's no treatment.

Those with SMA type II will start showing symptoms of the disease usually when they are between 6 and 18 months of age. These children can sit but will not be able to walk or stand without helped and without treatment, they might just lose their power to sit as well.

Children with SMA type III or Kugelberg-Welander disease start showing symptoms after they are 18 months of age and can walk on their own. They however, experience difficultly in walking or running and other such physical exercises related to legs.

Those with SMA type IV usually develop the symptoms after they are over 21 years of age ad have minor muscle weakness and other issues. It doesn't affect one's life expectancy.

The USA Food and Drug Administration has approved the Zolgensma gene therapy for children who show the signs of the disease and are less than 2 years. Last year in August, the FDA also gave its nod to the orally-administered drug risdiplam (Evrysdi) for patients who are older than two months of age and are diagnosed with SMA.

Physical therapy, occupational therapy, and rehabilitation are some measures that can be taken to help improve posture, stop joint immobility and help in case of muscle weakness and atrophy.

You can find the link to the crowdfunding page for baby Teera here.

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PM Modi Waives off Rs 6 Crore Tax on Imported Medicine for 6-month-old Baby Girl from Mumbai - News18

New Analysis Published in Psychiatry Research

SALT LAKE CITY, Feb. 08, 2021 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ:MYGN), a leader in genetic testing and precision medicine, announced today the peer-reviewed journal Psychiatry Research has published a new analysis showing the combinatorial approach available in the GeneSight Psychotropic test is better than single-gene testing at predicting patient outcomes and medication blood levels.

Myriads GeneSight test evaluates how variations in multiple genes may influence an individuals outcomes with certain FDA-approved medications commonly prescribed to treat depression, anxiety, and other psychiatric conditions.

Using data from the Genomics Used to Improve DEpression Decisions (GUIDED) randomized-controlled trial, the study evaluated the ability of the combinatorial approach available in the GeneSight Psychotropic test to predict patient outcomes and medication blood levels compared to Clinical Pharmacogenetics Implementation Consortium(CPIC) single-gene recommendations. CPIC recommendations are based on either CYP2C19 and CYP2D6, which are genes that are involved in how the body metabolizes medications commonly used to treat depression and other mental illnesses.

The study included two types of analyses:

Our analysis demonstrated the superior ability of combinatorial pharmacogenetic testing to predict variation in medication blood levels may result in improved patient outcomes, said lead author Anthony J. Rothschild, MD, the Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry at the University of Massachusetts Medical School. We believe this study provides compelling evidence of the clinical validity of the combinatorial pharmacogenomic test for patients with major depressive disorder, who have at least one prior medication failure.

This analysis demonstrates that the combinatorial approach of the GeneSight test more accurately predicts blood drug levels and identifies more patients with significant gene-drug interactions who would be missed by single-gene testing, said Dr. Mark Pollack, chief medical officer, Myriad Neuroscience. Combinatorial pharmacogenomics like the GeneSight test should become the standard-of-care to help physicians understand gene-drug interactions that could improve care for people with depression, anxiety and other conditions.

This is the second study evaluating the combinatorial approach of the GeneSight test to be published inPsychiatry Research.The earlier study, published in May 2020, demonstrated the combinatorial approach available in the GeneSight Psychotropic test was better at predicting citalopram and escitalopram blood concentrations when compared to single-gene testing.

The GUIDED study, the largest pharmacogenomic randomized controlled trial in mental health, showed that patients whose doctors received GeneSight results had significantly improved response and remission rates from depression, compared to treatment as usual.

About Myriad NeuroscienceMyriad Neuroscience is a business unit of Myriad Genetics, Inc., (NASDAQ: MYGN), a leader in genetic testing and precision medicine. Through its GeneSight Psychotropic test, Myriad Neuroscience provides information to healthcare providers about their patients genetic variations, which may impact how they metabolize or respond to certain psychiatric medications. Learn more at genesight.com/about-myriad-neuroscience/

About The GeneSight TestMyriads GeneSight Psychotropic test is the category-leading pharmacogenomic test for depression medications. The GeneSight test can help inform doctors about genes that may impact how patients metabolize or respond to certain psychiatric medications. It has been given to more than one million patients by tens of thousands of clinicians to provide genetic information that is unique to each patient. It supplements other information considered by a doctor as part of a comprehensive medical assessment. Learn more at GeneSight.com.

About Myriad GeneticsMyriad Genetics Inc., is a leading genetic testing and precision medicine company dedicated to transforming patient lives worldwide. Myriad discovers and commercializes genetic tests that determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. For more information on how Myriad is making a difference, please visit the Company's website:www.myriad.com.

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

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Companys strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties associated with COVID-19, including its possible effects on our operations and the demand for our products and services; our ability to efficiently and flexibly manage our business amid uncertainties related to COVID-19; the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decisions in Mayo Collab. Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), Assn for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013), and Alice Corp. v. CLS Bank Intl, 573 U.S. 208 (2014); risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2020, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

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GeneSight Psychotropic Test's Combinatorial Approach Proves Better than Single-Gene Testing at Predicting Patient Outcomes and Medication Blood Levels...

On June 26, 2000 in the East Room of the White House I stood at the podium and announced the sequencing of the human genome, a project accomplished by my relatively small team at company in only nine months. Seated behind me was President Clinton, and on a giant screen was U.K. Prime Minister Tony Blair. Francis Collins was on stage as the head of the National Institutes of Health human genome team. Seated in front of me were some of the senior scientists associated with human genome sequencing as well as top government officials and ambassadors from around the world. Behind the guests were 50 or so TV cameras and photographers. The entire event was being broadcast live around the world.

After years of never-ending work, criticism (from the outside world and even internally at my company), intervention by top science journal editors and even President Clinton, to be standing where history was being made that day was a very emotional and fulfilling experience. It was hard to believe we made it to this point though, and there was drama leading up to and even into the early hours of the morning. We all had to share drafts of our speeches the day before the event, and when I saw the speech from Prime Minister Blair, I told the head of the Office of Science and Technology Policy that I would not attend unless his speech was changed. I thought it was one-sided and contained disparaging remarks about me and my team. The White House science adviser said that they could not change a foreign head of governments speech. I said that if they wanted me to attend, they needed to do something. I received a call at 2 A.M. indicating that I would be very pleased with his speech, which I was indeed.

How did we get to this historic place? Genome sequencing discussions began in the mid 1980s that led to an NIH/Department of Energy genome effort that was getting funded with billions of dollars but was proceeding slowly by spreading the genome fragments over multiple labs around the world. My team at my first not-for-profit research institute, The Institute for Genomic Research or TIGR, was funded to do a small segment and assumed we would sit out the genome project.

In 1995, we published the first genome of a free-living organism, H. influenzae, in Science. This genome was sequenced using our new algorithm and automation to sequence a genome as a single project in months rather than years. I was certain that this approach would work with the human genome, but I was only one of a few who believed this. In 1998, my world changed with a call from Applied Biosystems (ABI) and their parent company offering $300 million for me to set up a new company to sequence the human genome with my technique and their new machine. I flew out to their headquarters in Foster City, Calif., to look at the prototype version of their new machine and was convinced it would work. We calculated that we would need 300 machines. On returning to TIGR, I told Ham Smith, Nobel laureate and my friend and colleague, what I saw and said that I had to go do this. His reply was: I dont think it will work, but I am going with you.

We started a new company called Celera Genomics with the goal of sequencing the first human genome in three years or less. The companys tagline was Speed Matters, Discovery Cant Wait. This announcement was not met with open arms by the NIH-led sequencing community who said Celeras sequencing plans would end up with the swiss cheese, CliffsNotes, Readers Digest or even Mad Magazine version of the genome. I guess I can understand why they were not thrilled to have a newcomer to the game and thus began what the press dubbed a race to sequencing the human genome pitting Celera against the NIH and international genome effort.

We knew the algorithm that we were using for bacterial genomes would not work for humans, nor would any of the existing computers. We had thousands of resumes sent to us, and fortunately one was from Eugene Myers, who ended up being one of the key heroes of the human genome. Gene, who was then a faculty member at the University of Arizona and had been the key developer of the BLAST tool for sequencing analysis, had been thinking about larger genome assembly and was encouraged by our success with bacterial genomes. Gene and a small team wrote 500,000 lines of computer code in a few months to create the Celera Assembler. Nine months later we had a complete human genome sequence and set out to annotate it to see what it said about us. We published our analysis in Science only after the late Don Kennedy, Science editor, stepped in to override leaders of the public project who had attempted to block our publication. The NIH effort published their data in Nature on the same day.

So, with the 20th anniversary of the publication of the first sequencing of the human genome on February 16, 2001, what do we have to show for the past two decades? The first decade post publication made steady progress in sequencing technology enabling more and more genomes of every class of life being sequenced, but unfortunately little effort has gone into generating knowledge and understanding about the human genome. This is due in part to the fact that significant funding in the United States at the government level has dwindled, while in other countries funding has increased. The good news is that essentially every new drug and vaccine is now based on genomics, and basic research has changed from sequencing genes to more function-based research.

Many thought that just by sequencing large numbers of genomes that understanding and new knowledge would fall into place. While that has helped with ancestry tracing and genome variation, there is still so much for us to learn and understand about how the genome codes for us humans.

Five years ago, I formulated a new approach combining comprehensive phenotyping with deep genome analysis using machine learning/artificial intelligence algorithms and other tools. The new approach came about because my genome showed that I was a heterozygote for the APOE gene, which confers a substantially increased risk for Alzheimers Disease. I convinced some neurologists at University of California, San Diego, to do an MRI brain scan and an MRI/PET scan for amyloid, thought to be a key marker for the disease. The good news for me personally was that both tests came back negative, but it showed me that I needed to combine clinical phenotype tests like the MRI with the genome to understand the predictive risk. This led to the formation of a new company called Human Longevity, Inc (HLI).

The goal of HLI was to offer the most comprehensive set of clinical tests for self-described healthy individuals that we could do in one day, such as whole-body MRI, cardiac CT scans, bone density, 4-D echo cardiac test and remote cardiac monitoring. We included a large array of chemical tests including the complete metabolome screening. The results of these integrated tests on so-called healthy people have been truly stunning. About 40 to 50 percent of people tested had significant disease of which they were unaware. Approximately 5 percent over 50 had a major tumor. The good news is they were almost all at early stages and could be removed or treated with radiation. About 1 percent of all tested had a brain aneurysm. Machine learning is providing new genome loci that correlate with diseases discovered. We are also looking for protective genetic markers for those like me with APOE changes but no Alzheimers, or women with BRCA mutations but no breast or ovarian cancers.

This notion of testing seemingly healthy people is not without critics. Some argue that if you look you will find something, and we might not have a cure or treatment for that disease, thus creating unnecessary distress. Or they say some tumors might be so slow-growing that treating them leads to unnecessary side effects; a wait and see is thus a better approach. As I have tried to show with my career, Im not satisfied with this. I believe that we have an obligation to utilize all the tools and knowledge we fought so hard to develop and uncover, including the one with the most potential, our human genome.

Overall, the practice of medicine needs to drastically change. We can prevent and predict diseases if we combine genomics on a grand scale with clinical phenotyping and machine learning. One factor impeding this progress is the fact that the health care system is incented to offer treatments but not prevention. With new clinical tools, cancers and other diseases can be detected at the earliest stages when treatments and potential cures are minimally invasive.

The genome will play a key role in the future bioeconomy, but the U.S. is already way behind. We are 54th in the world for sequence screening of new COVID-19 virus strains. And except for cancer, the genome is not a part of the practice of medicine. We all thought the genome sequence would allow us to understand ourselves and change medicine. That is happening too slowly, costing tens of millions of lives that could have been saved if we made it a national priority. One example is that it could be relatively easy to know who would be most susceptible to death from COVID-19 and flu. With the specter of more emerging infectious diseases, we need to act sooner rather than later.

When I stood at the podium at the White House press conference to announce the genome I said, The method used by Celera has determined the genetic code of five individuals. We have sequenced the genome of three females and two males, who have identified themselves as Hispanic, Asian, Caucasian or African American. We did this sampling not in an exclusionary way, but out of respect for the diversity that is America, and to help illustrate that the concept of race has no genetic or scientific basis. In the five Celera genomes, there is no way to tell one ethnicity from another. Society and medicine treats us all as members of populations, where as individuals we are all unique, and population statistics do not apply. I still stand by this statement. In fact, what we find today is that socioeconomic background contributes more to health access and outcomes than any other factor, biological or otherwise. The COVID-19 pandemic is a real-world, real-time example of this.

Progress is only made by daring to go where no roads currently exist. As President Clinton said at the White House event in 2000 to unveil the first survey of the human genome, this is the most important, most wondrous map ever produced by humankind. We need more explorers and more funding to fully utilize this map to uncover the new lands yet to be discovered in the human genome.

Originally posted here:

Reflections on the 20th Anniversary of the First Publication of the Human Genome - Scientific American