Category Archives: Gene Medicine

By: Dr. Francis Collins , National Institutes of Health

Anyone whos spent time with people affected by autism spectrum disorder (ASD) can tell you that its a very complex puzzle. The wide variability seen among individuals with this group of developmental brain disorders, which can disrupt communication, behavior control, and social skills, has also posed a huge challenge for researchers trying to identify underlying genetic and environmental factors. So, its no surprise that theres been considerable interest in the recent findings of the largest-ever genetic study of ASD.

In a landmark study that analyzed the DNA of more than 35,000 people from around the world, the NIH-funded international Autism Sequencing Consortium (ASC) identified variants in 102 genes associated with increased risk of developing ASD, up from 65 identified previously. Of the 102 genes, 60 had not been previously linked to ASD and 53 appeared to be primarily connected to ASD as opposed to other types of intellectual disability or developmental delay. It is expected that this newfound genetic knowledge will serve to improve understanding of the complex biological mechanisms involved in ASD, ultimately paving the way for new approaches to diagnosis and treatment.

The study reported in the journalCellwas led by Joseph Buxbaum, Icahn School of Medicine at Mount Sinai, New York; Stephan Sanders, University of California, San Francisco; Kathryn Roeder, Carnegie Mellon University, Pittsburgh, PA; and Mark Daly, Massachusetts General Hospital, Boston, MA and the Broad Institute of MIT and Harvard, Cambridge, MA. These researchers and their teams faced what might seem like a rather daunting task.

While common genetic variants collectively are known to contribute substantially to ASD, rare variants have been recognized individually as more major contributors to a persons risk of developing ASD. The challenge was how to find such rare variantswhether inherited or newly arising.

To do so, the researchers needed to analyze an enormous amount of DNA data. Fortunately, they and their ASC colleagues already had assembled a vast trove of data. Over the last decade, the ASC had collected DNA samples with full consent from thousands of people with and without ASD, including unaffected siblings and parents. All were aggregated with other studies, and, at the time of this investigation, they had gathered 35,584 unique samples. Those included more than 21,000 family-based samples and almost 12,000 samples from people diagnosed with ASD.

In search of rare genetic alterations, they sequenced whole exomes, the approximately 1.5 percent of the genome that codes for proteins. Their search produced a list of 102 ASD-associated genes, including 30 that had never been implicated in any developmental brain disorder previously.

But that was just the beginning. Next, the ASC team dug deeper into this list. The researchers knew from previous work that up to half of the people with ASD also have an intellectual disability or developmental delay. Many of the associated genes overlap, meaning they play roles in both outcomes. So, in one set of analyses, the team compared the list to the results of another genetic study of people diagnosed with developmental delays, including problems with learning or gross motor skills such as delayed walking.

The detailed comparison allowed them to discern genes that are more associated with features of ASD, as opposed to those that are more specific to these developmental delays. It turns out that 49 of the 102 autism-associated genes were altered more often in people with developmental delays than in those diagnosed with ASD. The other 53 were altered more often in ASD, suggesting that they may be more closely linked to this conditions unique features.

Further study also showed that people who carried alterations in genes found predominantly in ASD also had a better intellectual function. They also were more likely to have learned to walk without a developmental delay.

The 102 new genes fell primarily into one of two categories. Many play a role in the brains neural connections. The rest are involved primarily in switching other genes on and off in brain development. Interestingly, they are expressed both in excitatory neurons, which are active in sending signals in the brain and in inhibitory neurons that squelch such activity. Many of these genes are also commonly expressed in the brains cerebral cortex, the outermost part of the brain that is responsible for many complex behaviors.

Overall, these findings underscore that ASD truly does exist on a spectrum. Indeed, there are many molecular paths to this disorder. The ASC researchers continue to collect samples, so we can expect this list of 102 genes will continue to expand in the future.

With these gene discoveries in hand, the researchers will now also turn their attention to unraveling additional details about how these genes function in the brain. The hope is that this growing list of genes will converge on a smaller number of important molecular pathways, pointing the way to new and more precise ways of treating ASD in all its complexity.

Reference:

[1]Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An JY, Peng M, Collins R, Grove J, Klei L, Stevens C, Reichert J, Mulhern MS, Artomov M, Gerges S, Sheppard B, Xu X, Bhaduri A, Norman U, Brand H, Schwartz G, Nguyen R, Guerrero EE, Dias C; Autism Sequencing Consortium; iPSYCH-Broad Consortium, Betancur C, Cook EH, Gallagher L, Gill M, Sutcliffe JS, Thurm A, Zwick ME, Brglum AD, State MW, Cicek AE, Talkowski ME, Cutler DJ, Devlin B, Sanders SJ, Roeder K, Daly MJ, Buxbaum JD.Cell. 2020 Jan 23. {Epub ahead of print]

Links:

NIH Support: National Institute Mental Health; National Human Genome Research Institute

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Largest-Ever Genetic Study of Autism Yields New Insights - The Southern Maryland Chronicle

GERMANTOWN, Md. & HILDEN, Germany--(BUSINESS WIRE)--QIAGEN N.V. (NYSE: QGEN; Frankfurt Prime Standard: QIA) today announced the CE-marking and launch of its therascreen PIK3CA RGQ PCR Kit in Europe as an aid in identifying breast cancer patients with a PIK3CA mutation. Last year the therascreen PIK3CA test was approved by the FDA and launched as a companion diagnostic test for Piqray (alpelisib) in the US.

The therascreen PIK3CA test is a new diagnostic assay for detection of activating mutations in the phosphatidyl 3-kinase catalytic subunit alpha (PIK3CA) gene, and the first to enable testing of both DNA from FFPE tissue or plasma specimens. All QIAGEN therascreen PIK3CA tests leverage QIAGENs worldwide co-exclusive license from Johns Hopkins University for PCR-based companion diagnostics based on detection of mutations in the PIK3CA gene.

1 in 8 women in Europe will develop breast cancer before the age of 85, making it the most common form of cancer in female patients. The therascreen assay detects 11 clinically actionable PIK3CA mutations, which are estimated to be present in approximately 40% of hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+ HER2-) advanced breast cancer cases.

This launch in Europe further underscores our commitment to support patients with breast cancer, the most common cancer in female cancer patients, with an estimated incidence of 562,500 in Europe in 2018 according to the WHO said Jonathan Arnold, Vice President, Head of Oncology and Precision Diagnostics. We are convinced that our therascreen PIK3CA Kit, which expands our market-leading therascreen portfolio of companion diagnostics, will provide a valuable testing option for those seeking new ways to combat advanced breast cancer. We are committed to making the therascreen PIK3CA Kit available immediately so that leading laboratories in Europe can provide patients with the test as soon as possible.

Please find the full press release here

Additional information can be found at http://www.qiagen.com/cmp/mdx/pik3ca-rgq-pcr-kit-row/

Excerpt from:
QIAGEN Launches FFPE and Liquid Biopsy PIK3CA Diagnostics in Europe to Enhance Precision Medicine in Advanced Breast Cancer - Business Wire

AI is rocking medical diagnosis with its potential to incite drastic improvements to hospital processes. AI can process images and patient health records with more accuracy and expediency than humans are capable of, lessening physician workload, reducing misdiagnosis, and empowering clinical staff to provide more value.

While early moving hospitals are already extracting value from AI in medical diagnosis, most US hospitals are at the very early stage of the AI transformation curve - and they risk falling behind if they don't move now.

In this report, Business Insider Intelligence examines the value of AI applications in three high-value areas of medical diagnosis - imaging, clinical decision support, and personalized medicine - to illustrate how the tech can drastically improve patient outcomes, lower costs, and increase productivity.

We look at US health systems that have effectively applied AI in these use cases to illustrate where and how providers should implement AI. Finally, we examine how a leading US health system validates AI partners and internally organizes its AI strategy to offer provider organizations a template for AI innovation.

The companies mentioned in this report are: Aidoc, Allscripts, Amazon, Arterys, Boston Gene, Cabell Huntington Hospital, Cerner, Cleveland Clinic, Epic, Geisinger Health System, Google, HCA Healthcare, IBM, iCAD, IDx, Intermountain Healthcare, Johns Hopkins, Meditech, Microsoft, Mount Sinai, NorthShore University HealthSystem, Oak Street Health, Stanford University, Tempus, UCI Health System, Unanimous AI, Verily, Viz.ai, and Yale New Haven Hospital.

Here are some of the key takeaways from the report:

In full, the report:

Want to learn more about the fast-moving world of digital health? Here's how to get access:

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AI IN MEDICAL DIAGNOSIS: How top US health systems are reacting to the disruptive force of AI by revolutionizi - Business Insider India

RESEARCH TRIANGLE PARK, N.C. , Feb. 04, 2020 (GLOBE NEWSWIRE) -- Asklepios BioPharmaceutical (AskBio), a clinical-stage adeno-associated virus (AAV) gene therapy company, and its NanoCor Therapeutics subsidiary today announced that the first patient has been dosed in a Phase 1 clinical trial of NAN-101. NAN-101 is a gene therapy that aims to activate protein phosphatase inhibitor 1 (I-1c) to inhibit the activity of protein phosphatase 1 (PP1), a substance that plays an important role in the development of heart failure.

Congestive heart failure (CHF) is a condition in which the heart is unable to supply sufficient blood and oxygen to the body and can result from conditions that weaken the heart muscle, cause stiffening of the heart muscles, or increase oxygen demand by the body tissues beyond the hearts capability.

"Dosing the first patient using gene therapy to target I-1c to improve heart function is a tremendous milestone not only for the AskBio and NanoCor teams but, more importantly, for patients whose quality of life is negatively affected by CHF, said Jude Samulski, PhD, Chief Scientific Officer and co-founder of AskBio. We initially developed this gene therapy as treatment for late-stage Duchenne muscular dystrophy patients who typically die from cardiomyopathy. Following preclinical studies, we observed that heart function improved, which led us to investigate treatment for all types of heart failure.

Were excited to be involved in this novel approach for patients with Class III heart failure, said Timothy Henry, MD, FACC, MSCAI, Lindner Family Distinguished Chair in Clinical Research and Medical Director of The Carl and Edyth Lindner Center for Research at The Christ Hospital in Cincinnati, Ohio, and principal investigator for the study. These patients currently have no other options besides transplant and left ventricular assist devices (LVAD). Today, we started to explore the potential of gene therapy to change their outcomes.

Heart disease is the leading cause of death worldwide, with CHF affecting an estimated 1% of the Western world, including over six million Americans. There is no cure, and medications and surgical treatments only seek to relieve symptoms and slow further damage.

Research by many investigators around the world has been trying to understand what exactly goes wrong in the heart and weakens its pumping activity until it finally fails, said Evangelia (Litsa) Kranias, PhD, FAHA, Hanna Professor, Distinguished University Research Professor and Director of Cardiovascular Biology at the University of Cincinnati College of Medicine. The aim has been to identify potential therapeutic targets to restore function or prevent further deterioration of the failing heart. Along these lines, research on the role of I-1c started over two decades ago, and it moved from the lab bench to small and large animal models of heart failure. The therapeutic benefits at all levels were impressive. It is thrilling to see I-1c moving into clinical trials with the hope that it also improves heart function in patients with CHF.

About the NAN-101 Clinical Trial NAN-CS101 is a Phase 1 open-label, dose-escalation trial of NAN-101 in subjects with NYHA Class III heart failure. NAN-101 is administered directly to the heart via an intracoronary infusion by cardiac catheterization in a process similar to coronary angioplasty, commonly used to deliver treatments such as stem cells to patients with heart disease. The primary objective of the study is to assess the safety of NAN-101 for the treatment of NYHA Class III heart failure, as well as assess the impact of this treatment on patient health as measured by changes in exercise capacity, heart function and other factors including quality of life.

AskBio is actively enrolling patients with NYHA Class III heart failure to assess three doses of NAN-101. Please refer to clinicaltrials.gov for additional clinical trial information.

Would you like to receive our AskFirst patient engagement program newsletter? Sign up at https://www.askbio.com/patient-advocacy.

About The Christ Hospital Health Network The Christ Hospital Health Network is an acute care hospital located in Mt. Auburn with six ambulatory centers and dozens of offices conveniently located throughout the region. More than 1,200 talented physicians and 6,100 dedicated employees support the Network. Its mission is to improve the health of the community and to create patient value by providing exceptional outcomes, the finest experiences, all in an affordable way. The Network has been recognized by Forbes Magazine as the 24th best large employer in the nation in the magazines Americas 500 Best Large Employers listing and by National Consumer Research as the regions Most Preferred Hospital for more than 22 consecutive years. The Network is dedicated to transforming care by delivering integrated, personalized healthcare through its comprehensive, multi-specialty physician network. The Christ Hospital is among only eight percent of hospitals in the nation to be awarded Magnet recognition for nursing excellence and among the top five percent of hospitals in the country for patient satisfaction. For more than 125 years, The Christ Hospital has provided compassionate care to those it serves.

About AskBioFounded in 2001, Asklepios BioPharmaceutical, Inc. (AskBio) is a privately held, clinical-stage gene therapy company dedicated to improving the lives of children and adults with genetic disorders. AskBios gene therapy platform includes an industry-leading proprietary cell line manufacturing process called Pro10 and an extensive AAV capsid and promoter library. Based in Research Triangle Park, North Carolina, the company has generated hundreds of proprietary third-generation AAV capsids and promoters, several of which have entered clinical testing. An early innovator in the space, the company holds more than 500 patents in areas such as AAV production and chimeric and self-complementary capsids. AskBio maintains a portfolio of clinical programs across a range of neurodegenerative and neuromuscular indications with a current clinical pipeline that includes therapeutics for Pompe disease, limb-girdle muscular dystrophy type 2i/R9 and congestive heart failure, as well as out-licensed clinical indications for hemophilia (Chatham Therapeutics acquired by Takeda) and Duchenne muscular dystrophy (Bamboo Therapeutics acquired by Pfizer). For more information, visit https://www.askbio.com or follow us on LinkedIn.

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AskBio Announces First Patient Dosed in Phase 1 Trial Using AAV Gene Therapy for Congestive Heart Failure - BioSpace

NEW YORK, Feb. 4, 2020 /PRNewswire/ --Hoth Therapeutics, Inc. (NASDAQ:HOTH), a biopharmaceutical company focused on unique targeted therapeutics for patients suffering from dermatological indications ranging from atopic dermatitis, psoriasis and acne along with gene therapy treatment for asthmatics, is pleased to announce the initiation of a preclinical study for the treatment of asthma and allergic inflammation in collaboration withNorth Carolina State University(NC State).

The study has begun thedelivery and distribution of nebulized particleswhich willenable the therapeutic oligonucleotide (oligo), short DNA and RNA molecules that have a wide range of applications in gene testing.Hoth has appointed Dr. Glenn Cruse to its Scientific Advisory Board and will oversee the Company's gene therapy programs advancements.

Mr.Robb Knie, Chief Executive Officer of Hoth Therapeutics, Inc. commented,"We are extremely pleased that our gene therapy program with NC State has officially begun and that Dr. Cruse who is overseeing the advancement ofexperimentshas joined our Scientific Advisory Board. Commencement of this initiative is an important step in the development and growth of our company. Dr. Cruse's expertise asa leading mast cell biologist in allergic and inflammatory diseases will be invaluable for the preclinical development of Splice-switching oligonucleotides (SSOs) for asthma."

In November 2019 Hoth entered into a licensing agreement with North Carolina State University (NC State) to study NC State's Exon Skipping Approach for Treating Allergic Diseases. This Exon Skipping Approach was developed by Dr. Glenn Cruse, Principal Investigator and Assistant Professor in the Department of Molecular Biomedical Sciences at the NC State College of Veterinary Medicine. During Dr. Cruse's research, a new approach for the technique of antisense oligonucleotide-mediated exon skipping to specifically target and down-regulate IgE receptor expression in mast cells was identified. These findings set a breakthrough for allergic diseases as they are driven by the activation of mast cells and the release of mediators in response to IgE-directed antigens.

Glenn Cruse completed his Ph.D. at Glenfield Hospital, The University of Leicester, UK in 2009. He then moved to the National Institutes of Health in Bethesda, Maryland in January 2010 to start a visiting postdoctoral fellowship in the Laboratory of Allergic Diseases, NIAID, In January 2015, Dr. Cruse was appointed as a Research Fellow in the same laboratory. Dr. Cruse joined the Department of Molecular Biomedical Sciences at NC State in January 2016 as an Assistant Professor.

Dr. Cruse is a mast cell biologist that has authored and co-authored over 30 publications including articles in top journals such as the New England Journal of Medicine, Proceedings of the National Academy of Sciences USA and Immunity. The Cruse lab is interested in the role that mast cells play in allergic and inflammatory diseases and identifying novel therapeutics that target mast cells. Since mast cells act as sentinel cells that participate in both innate and acquired immunity, particularly at biological barriers, emphasis on diseases in tissues at the interface with the environment such as the lung, skin, gastrointestinal tract and even the neuro-immune axis are the main focus of the lab.

About Hoth Therapeutics, Inc.Hoth Therapeutics, Inc. isa clinical-stage biopharmaceutical company focused on developing new generation therapies for dermatological disorders. HOTH's pipeline has the potential to improve the quality of life for patients suffering from indications including atopic dermatitis, chronic wounds, psoriasis, asthma and acne. To learn more, please visitwww.hoththerapeutics.com.

Forward Looking StatementsThis press release includes "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements in this press release include, but are not limited to, statements that relate to the advancement and development of the BioLexa Platform, the commencement of clinical trials, the availability of data from clinical trials and other information that is not historical information. When used herein, words such as "anticipate", "being", "will", "plan", "may", "continue", and similar expressions are intended to identify forward-looking statements. In addition, any statements or information that refer to expectations, beliefs, plans, projections, objectives, performance or other characterizations of future events or circumstances, including any underlying assumptions, are forward-looking. All forward-looking statements are based upon Hoth's current expectations and various assumptions. Hoth believes there is a reasonable basis for its expectations and beliefs, but they are inherently uncertain. Hoth may not realize its expectations, and its beliefs may not prove correct. Actual results could differ materially from those described or implied by such forward-looking statements as a result of various important factors, including, without limitation, market conditions and the factors described under the caption "Risk Factors" in Hoth's Form 10K for the period endingDecember 31, 2018, and Hoth's other filings made with the Securities and Exchange Commission. Consequently, forward-looking statements should be regarded solely as Hoth's current plans, estimates and beliefs. Investors should not place undue reliance on forward-looking statements. Hoth cannot guarantee future results, events, levels of activity, performance or achievements. Hoth does not undertake and specifically declines any obligation to update, republish, or revise any forward-looking statements to reflect new information, future events or circumstances or to reflect the occurrences of unanticipated events, except as may be required by law.

ContactsInvestor Relations Contact:Phone: (646) 756-2997Email:investorrelations@hoththerapeutics.comwww.hoththerapeutics.com

KCSA Strategic CommunicationsValter Pinto (212) 896-1254Hoth@kcsa.com

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Hoth Initiates Preclinical Gene Therapy Program with NC State for the Treatment of Asthma and Allergic Inflammation - P&T Community

Researches at UCSD Health Sciences identify gene with functional role in aging of eye

San Diego Community News Group

A lengthy-named gene called Elongation of Very Long Chain Fatty Acids Protein 2 or ELOVL2 is an established biomarker of age. In a new paper, published online Jan. 14, 2020 in the journal Aging Cell, researchers at the University of California San Diego School of Medicine say the gene appears to play a key role in age-associated functional and anatomical agingin vivoin mouse retinas, a finding that has direct relevance to age-related eye diseases.

Specifically, the research team, led by senior author Dorota Skowronska-Krawczyk, Ph.D., assistant professor in the Viterbi Family Department of Ophthalmology at UC San Diego Shiley Eye Institute, found that an age-related decrease in ELOVL2 gene expression was associated with increased DNA methylation of its promoter. Methylation is a simple biochemical process in which groups of carbon and hydrogen atoms are transferred from one substance to another. In the case of DNA, methylation of regulatory regions negatively impacts the expression of the gene.

When researchers reversed hypermethylationin vivo, they boosted EVOVL2 expression and rescued age-related decline in visual function in mice. These findings indicate that ELOVL2 actively regulates aging in mouse retina, provides a molecular link between polyunsaturated fatty acids elongation and visual functions, and suggests novel therapeutic strategies for treatment of age-related eye diseases, wrote the authors.

ELOVL2 is involved in production of long-chain omega-3 and omega-6 polyunsaturated fatty acids, which are used in several crucial biological functions, such as energy production, inflammation response and maintenance of cell membrane integrity. The gene is found in humans as well as mice.

In particular, ELOVL2 regulates levels of docosahexaenoic acid or DHA, a polyunsaturated omega-3 fatty acid abundantly found in the brain and retina. DHA is associated with a number of beneficial effects. Notably, its presence in photoreceptors in eyes promotes healthy retinal function, protects against damage from bright light or oxidative stress and has been linked to improving a variety of vision conditions, from age-related macular (AMD) degeneration to diabetic eye disease and dry eyes.

Skowronska-Krawczyk said the work demonstrated for the first time that a methylation clock gene had a functional role in the aging of an organ. In this case, the eye. DNA methylation is used throughout the human body, essentially turning biological switches on and off to maximize efficient operation. It has key regulatory roles in the bodys cardiovascular, neurological, reproductive and detoxification systems.

In recent years, there has been much work and progress in identifying possible biomarkers that predict the biological age (not chronological) of individuals. Such biomarkers would be useful in identifying risk and status of age-related diseases. ELOVL2 is among the genes attracting greatest interest.

I have been asked whether I think ELOVL2 istheaging gene, said Skowronska-Krawczyk. After thinking about it, it is not unreasonable to think that lower ELOVL2 expression might be at the basis for many age-related conditions. Future work in our lab will address that question.

For the full study, visithttps://onlinelibrary.wiley.com/doi/full/10.1111/acel.13100

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Researches at UCSD Health Sciences identify gene with functional role in aging of eye - A lengthy-named gene called Elongation of Very Long Chain...