The CDC estimates that sickle cell disease affects well over 100,000 Americans, with the disease occurring most often in African Americans. September has been designated as National Sickle Cell Awareness month designed to focus attention on the ongoing research in this field and the need for new treatments. The sector can certainly point to the significant progress that has taken place during the past few years, with new medicines reaching the market and several novel therapeutics with new mechanisms of action advancing in the pipeline.

Ted Love, president and CEO of Global Blood Therapeutics Inc. (GBT), said 2019 was a landmark year with the FDA approval of two new novel therapies to treat sickle cell disease. He was speaking at the virtual annual Sickle Cell Disease (SCD) Therapeutics Conference this week. His company, together with the Sickle Cell Disease Association of America, was hosting the one-day event featuring discussions on the latest advances and future trends.

Approvals

The key manifestation of the inherited blood disorder is that red blood cells (RBCs) are abnormally shaped (crescent), which restricts their flow in blood vessels and limits oxygen delivery to the bodys tissues, leading to severe pain and organ damage. The condition is also characterized by severe chronic inflammation that results in vaso-occlusive crisis (VOC) where patients experience episodes of extreme pain and organ damage.

Late November, GBT gained accelerated approval for its Oxbryta (voxelotor) tablets for the treatment SCD in adults and pediatric patients 12 and older. The agencys green light came less than two weeks after it gave the go-ahead to Novartis AG for Adakveo (crizanlizumab) to reduce the frequency of VOCs in adult and pediatric patients ages 16 and older with SCD.

According to Love, Oxbryta is a new class of therapy binding to hemoglobin and stabilizing RBCs in an oxygenated state and inhibiting deoxygenated sickle hemoglobin polymerization, making cells less likely to bind together and form the distinctive sickle shape.

The launch of the drug has gone well since it was approved, he said in the companys second-quarter financial report and business update, despite the impact of COVID-19. Net sales in the period reached $31.5 million, well ahead of the Streets expectations. Going forward, the company is planning to expand the potential use of Oxbryta for the treatment of SCD in children as young as 4 years old and also seek marketing authorization in Europe for Oxbryta to treat hemolytic anemia in SCD patients ages 12 and older with a marketing authorization application being submitted to the EMA by the middle of next year.

Pipeline progress

Cambridge, Mass.-based Agios Pharmaceuticals Inc. is working on mitapivat (AG-348), an investigational, oral, small-molecule allosteric activator of wild-type and a variety of mutated pyruvate kinase-R (PKR) enzymes, in patients with SCD. The compound has been shown to decrease 2,3-diphosphoglycerate (2,3-DPG) and increase adenosine triphosphate (ATP), and through that mechanism, it may reduce hemoglobin (Hb) S polymerization and red blood cell sickling. In June, the company reported that clinical proof of concept had been established based on a preliminary analysis in a phase I trial being conducted in collaboration with the U.S. NIH as part of a cooperative research and development agreement.

The ongoing study had enrolled nine patients, with eight completing all planned dose levels of mitapivat. Seven of eight patients who completed all dose levels experienced a Hb increase, with five of eight patients (63%) achieving a hemoglobin increase of 1 g/dL from baseline (range 1-2.7 g/dL). All five patients who achieved a hemoglobin increase of 1 g/dL did so at doses of 50 mg BID or lower. Decreases in 2,3-DPG and increases in ATP levels were observed, consistent with the proposed mechanism of action and comparable to that observed in healthy volunteer studies with mitapivat.

The company said it expects to report data from ACTIVATE and ACTIVATE-T, its two global pivotal trials for mitapivat in adults with pyruvate kinase deficiency, between the end of 2020 and mid-2021.

Watertown, Mass.-based Forma Therapeutics Holdings Inc., which made its public debut this year, also has a selective RBC pyruvate kinase-R activator in its pipeline for treating SCD. FT-4202 is being evaluated in a phase I trial in SCD patients ages 12 and older and has been granted fast track, rare pediatric and orphan drug designations. The compound is a potent activator of pyruvate kinase-R designed to improve RBC metabolism, function and survival by decreasing 2,3 DPG and increasing ATP, potentially resulting in both increased hemoglobin levels and reduced VOCs.

Olinciguat, an oral guanylate cyclase (sGC) stimulator, being developed by Cyclerion Therapeutics Inc., has completed the treatment period in its STRONG-SCD study with a total of 70 patients randomized. The placebo-controlled, dose-ranging study is designed to evaluate safety, tolerability and pharmacokinetics, as well as to explore effects on daily symptoms and biomarkers of disease activity when dosed over a 12-week treatment period. Top-line results are expected this year. Olinciguat is a compound that aims to stimulate sGC production, leading to the production of a signaling molecule called cyclic guanosine monophosphate (cGMP). High levels of cGMP help reduce inflammation in blood vessels, decrease adhesion between RBCs, and allow for improved blood flow by increasing the availability of nitric oxide.

Boston-based Imara Inc. is developing IMR-687, a small-molecule inhibitor of PDE9 that degrades cyclic guanosine monophosphate (cGMP), an active signaling molecule that plays a role in vascular biology. The company said that lower levels of cGMP are often found in people with SCD and beta-thalassemia and are associated with impaired blood flow, increased inflammation, greater cell adhesion and reduced nitric oxide-mediated vasodilation. Blocking PDE9 acts to increase cGMP levels, which are associated with reactivation of fetal hemoglobin.

In August, the company dosed the first patient in its Ardent phase IIb trial of IMR-687 for adult patients with SCD. The planned primary efficacy objective is to evaluate the proportion of all patients with fetal hemoglobin (HbF) response, defined as an increase of 3% in HbF from baseline to week 24, compared to placebo.

Gene therapy/gene editing

Since SCD is a monogenic disease condition, researchers believe that it would be a good candidate for gene therapy therapeutic approaches. For example, significant progress is being made by Cambridge, Mass.-based Bluebird Bio Inc. with lentiglobin, its lentiviral-based gene therapy that inserts an anti-sickling beta-globin variant into CD34-positive cells, progenitors of red blood cells.

At the virtual European Hematology Association (EHA) meeting in June, it reported new data from its ongoing phase I/II study involving adult and adolescent patients with SCD that showed a near-complete reduction of serious VOCs and acute chest syndrome. The company expects to submit a BLA to the FDA for the gene therapy next year.

Crispr Therapeutics AG and Vertex Pharmaceuticals Inc. are progressing CTX-001, an investigational, autologous, CRISPR/Cas9 gene-edited hematopoietic stem cell therapy being evaluated for patients suffering from severe hemoglobinopathies. At EHA, the companies reported that in the phase I/II Climb-121 study, at nine months after CTX-001 infusion, the first treated patient was free of VOCs, was transfusion independent and had total hemoglobin levels of 11.8 g/dL, 46.1% fetal hemoglobin and F-cells (erythrocytes expressing fetal hemoglobin) of 99.7%.

Last month, Cambridge, Mass.-based Editas Medicine Inc., a genome editing company, reported that the FDA had granted rare pediatric disease designation for EDIT-301, an experimental, autologous cell medicine, being developed as a potentially best-in-class, durable medicine for SCD. The company plans to file an investigational new drug application for EDIT-301 by the end of this year. EDIT-301 comprises sickle patient CD34+ cells genetically modified using a hCRISPR/Cas12a (also known as Cpf1) ribonucleoprotein to edit the HBG1/2 promoter region in the beta-globin locus. Red blood cells derived from EDIT-301 CD34+ cells demonstrate a sustained increase in fetal hemoglobin (HbF) production.

In its second-quarter financial report and business update, Beam Therapeutics Inc. announced the nomination of its first two adenine base editing development candidates, BEAM-101, targeting patients with hereditary persistence of fetal hemoglobin, and BEAM-102 (Makassar variant), both aimed at correcting SCD.

New Initiative

The NIH, which reports it spends approximately $100 million on sickle cell disease research, announced that is has launched The Cure Sickle Cell Initiative designed to speed the development of cures for the disease. It will take advantage of the latest genetic discoveries and technological advances to progress the most promising genetic-based curative therapies safely into clinical trials within five to 10 years.

Aided by research partners, the initiative will establish a national data warehouse of genetic therapies for sickle cell disease and conduct comparative analyses of therapeutic approaches to assess both clinical and cost effectiveness. National networks will also be created to make it easier for patients and providers to interact with the research, clinical trials, and other activities.

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New medicines in the pipeline to treat sickle cell disease - BioWorld Online

Depression is a dark horse.

The disease often goes unnoticed, but affects work performance, social interaction and the ability to take pleasure in everyday life. According to theNational Center for Biotechnology Information, antidepressants only help around 50 percent of those who struggle with depression and anxiety and, even when they are effective, scientists have yet to understand how they work in the brain.

MSU associate professor of physiology A.J. Robison and his lab used new CRISPR-based technology to uncover pathways of depression-like behavior in the mouse brain. Credit: College of Natural Science

But groundbreaking research in the lab of Michigan State University scientistA.J. Robison, associate professor in theDepartment of Physiologyand MSUsNeuroscience Program, is directing some new rays of light onto the molecular, cellular and circuit-level mechanisms underlying depression-like diseases.

Theresultswere recently published inNature Communications.

In this paper, we perform the first ever CRISPR-based gene editing [a genetic engineering technique in molecular biology by which the genomes of living organisms may be modified] in a single circuit between two areas of the mouse brain, explained Robison about the culmination of five years of research funded by the National Institutes of Mental Health. We can reach into the mouse brain and manipulate specific genes in a circuit involved in depression and anxiety-like behaviors a critical advance on the road to genetic medicine for psychiatric diseases.

Scientists estimate there are roughly 80-100 billion neurons connecting regions of the brain. To accomplish the feat of locating and manipulating a single gene in a single circuit required new and sophisticated technology. With the expertise of co-author Rachael Neve, director of theGene Transfer Core at Massachusetts General Hospital, they developed it.

The key advance is that we designed a dual-vector system to manipulate a specific gene in the connections between two brain areas, and that has never been done before, Robison said.

Cross section of a mouse brain. The projections of the cells between the vHPC and NAc, shown here in neon green, are manipulated by the new CRISPR viral vector-based technology developed by Rachael Neve and the Robison Lab. Credit: Andrew Eagle

The neurons that Robison and his team zeroed in on originate in the ventral hippocampus (vHPC), a deep-seated structure that projects to regions in the brain important in stress susceptibility, mood and social avoidance. Neurons rooted in the vHPC reach out with branch-like structures called axons to connect with the nucleus accumbens, or NAc. The completed circuit is regulated by the star of the pioneering paper, the transcription factor known as DFosB.

Using the viral vector technology specifically designed and packaged by Neve, the team split the CRISPR system in half. Half of the system, inert on its own, was an enzyme that can mutate DNA in the vHPC. The other half, a guide RNA, was sent to all cells that project to the NAc and tells the enzyme where to bind and the specific gene to mutate. Only those cells specific to the circuit from the vHPC to the NAc got both halves, triggering the enzyme to bind with and turn off a single gene: FosB.

When the FosB gene was turned off in the neurons, we were able to get a circuit-specific behavioral effect relevant to a disease like depression, said Robison about the landmark discovery. When we put it back, or rescued it within the circuit, the effect was erased.

Claire Manning was a key contributor to the groundbreaking study and is now a postdoctoral researcher at Stanford University. Credit: Ken Moon

One of the most exciting findings from our investigations was the circuit-specific role of the FosB protein in conferring resilience to stress, Eagle said. We also discovered that FosB altered the excitability of hippocampal circuit neurons and may be affecting long-term downstream changes that lead to changes in the activity of this circuit. But removing DFosB permanently altered the expression of a suite of genes, in effect removing the conductor from the orchestra. To that end, the paper goes on to report in-depth experiments on DFosB largely done by the members of theRobison Labincluding co-first authorsClaire Manning, a 2019 neuroscience graduate, now a postdoc at Stanford University; andAndrew Eagle, a former postdoctoral researcher, now an assistant professor in the MSU Department of Physiology.

Andrew Eagle, shown here imaging a mouse brain, played a major role in conducting experiments to further probe the function of DFosB. Credit: Research@MSU.

Based on the findings in the paper, the Robison Lab will continue to develop highly collaborative and cutting-edge techniques, accelerated by MSUs newly completed Interdisciplinary Science and Technology Building. This work is important because it elucidates a potential mechanism, namely FosB, for how stress may contribute to depression, Eagle continued. Future clinical work may find ways to directly manipulate FosB, or more likely one of its gene targets, to provide resilience to stress and decrease the incidence of depression in vulnerable people.

The end of this paper, which shows us measuring the changes of expression in hundreds of genes when we remove DFosB, is only the beginning of years of work for our lab, Robison said. Which genes are important and what are they doing in the brain? This is the challenge of a lifetime for me and my lab.

This article is repurposed content originally featured on the College of Natural Sciences website.

Link:
Illuminating the opaque pathways of depression - MSUToday

-- Webcast conference call to be held on Monday, Sept. 28, 2020 at 8:30 a.m. Eastern Time --

-- Additional poster presentations at WMS will highlight data from Sareptas RNA and gene therapy programs --

CAMBRIDGE, Mass., Sept. 14, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that new data from its most advanced gene therapy programs will be presented at the WMS25 Virtual Congress, the 25th International Annual Congress of the World Muscle Society, being held Sept. 28 Oct. 2.

Sarepta will host a webcast and conference call on Monday, Sept. 28, 2020 at 8:30 a.m. ET, to discuss the results, which include two-year functional data from Study 101 of SRP-9001 for Duchenne muscular dystrophy and 18-month functional results from Cohort 1 in the study of SRP-9003 for Limb-girdle muscular dystrophy Type 2E.

This will be webcast live under the investor relations section of Sarepta's website at https://investorrelations.sarepta.com/events-presentationsand will be archived there following the call for one year. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary. The conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 6793650. Please specify to the operator that you would like to join the "Long-term Functional Data from Sareptas Gene Therapy Programs call.

In total, Sarepta will present 16 abstracts at this years meeting. All posters will be available on-demand throughout the Congress beginning on Monday, Sept. 28 at 7:00 a.m. EST. The full WMS25 Virtual Congress program is available here: https://www.wms2020.com/programme/.

Gene Therapy:

RNA Platform:

Natural history and other presentations:

Presentations will be archived under the events and presentations section of the Sarepta Therapeutics website at http://www.sarepta.comforone year following their presentation at WMS25.

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

Internet Posting of Information

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

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

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

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

Original post:
Long-term functional data from Sarepta Therapeutics' Most Advanced Gene Therapy Programs to be Presented at Upcoming Annual Congress of the World...

SAN DIEGO, Sept. 14, 2020 /PRNewswire/ -- Locanabio, Inc., a leader in RNA-targeted gene therapy, today announced that results from a preclinical study of the company's therapeutic systems for the potential treatment of myotonic dystrophy type 1 (DM1) were published in Nature Biomedical Engineering. For the full article, titled "The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy," please visit: https://www.nature.com/articles/s41551-020-00607-7

Scientists at Locanabio, working with academic collaborators at UC San Diego School of Medicine and the University of Florida, assessed whether an RNA-targeting CRISPR Cas9 system (RCas9) could provide molecular and functional rescue of dysfunctional RNA processing in a DM1 mouse model. The RCas9 system was administered with one dose of an AAV gene therapy vector. Results in both adult and neonatal mice and using both intramuscular and systemic delivery showed prolonged RCas9 expression even at three months post-injection with efficient reversal of molecular (elimination of toxic RNA foci, MBNL1 redistribution, reversal of splicing biomarkers) and physiological (myotonia) features of DM1.Importantly, there were no significant adverse responses to the treatment.

"These results are consistent with earlier findings from several in vitro studies in muscle cells derived from DM1 patients published by Locanabio's scientific co-founder Dr. Gene Yeo of UC San Diego and further indicate the significant potential of our RNA-targeting gene therapy as a DM1 treatment," said Jim Burns, Ph.D., Chief Executive Officer at Locanabio. "Data show that our RNA-targeting system is able to destroy the toxic RNA at the core of this devastating genetic disease and thereby correct the downstream molecular and biochemical changes that result in myotonia, which is a hallmark symptom of DM1. We are pleased that Nature Biomedical Engineering recognizes the value of these preclinical data and we look forward to further advancing this developmental program to the benefit of DM1 patients."

"Currently available treatments for DM1 can improve specific symptoms but do not target the underlying biology and cause of the disease. These data demonstrate that RNA-targeting systems may efficiently and specifically eliminate toxic RNA repeats that cause DM1 and potentially lead to a more effective treatment option for patients," said Dr. Yeo. "The results also indicate that RNA-targeting gene therapy has potential applications in the treatment of other diseases, such as Huntington's disease and certain genetic forms of ALS, which are also caused by a buildup of toxic RNA repeats."

These studies were funded in part by the Muscular Dystrophy Association (MDA). "We are delighted to support Locanabio's recent work in myotonic dystrophy. These preclinical results represent a promising advance and a novel scientific approach for a group of patients who represent a major unmet medical need," said Sharon Hesterlee, Ph.D., Chief Research Officer, MDA.

About Locanabio, Inc.

Locanabio is the global leader in developing a new class of genetic medicines. Our unique and multi-dimensional approach uses gene therapy to deliver RNA binding protein-based systems to correct the message of disease-causing RNA and thereby change the lives of patients with devastating genetic diseases. These broad capabilities delivered via gene therapy enable Locanabio to potentially address a wide range of severe diseases with a single administration. The company is currently advancing programs in neuromuscular, neurodegenerative and retinal diseases. For more information, visit http://www.locanabio.com.

About Myotonic Dystrophy

Myotonic dystrophy type 1 (DM1) is an autosomal dominant genetic disorder affecting skeletal muscle, cardiac muscle, the gastrointestinal tract, and the central nervous system. DM1 is caused by a mutation in the myotonic dystrophy protein kinase (DMPK) gene. This mutation leads to a repeat expansion of the CTG (cytosine-thymine-guanine) trinucleotide. The expanded CTG is transcribed into toxic CUG (cytosine-uracil-guanine) repeats in the DMPK messenger RNA (mRNA). These toxic mRNA repeats lead to disease symptoms including progressive muscle wasting, weakness and myotonia (delayed relaxation of skeletal muscle), a hallmark of DM1. The incidence of myotonic dystrophy has historically been estimated at one in 8,000 individuals worldwide or approximately 40,000 people in the United States.

Media Contact

Brian ConnorBerry & Company[emailprotected]+1-845-702-2620

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Treatment with RNA-Targeting Gene Therapy Reverses Molecular and Functional Features of Myotonic Dystrophy Type 1 in Mice - PRNewswire

CAMBRIDGE, Mass., Sept. 09, 2020 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that it has completed a Type C written response only meeting with the Office of Tissues and Advanced Therapies (OTAT), part of the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration (FDA), to obtain OTATs concurrence on the commencement of its next clinical trial for SRP-9001 using commercial process material. SRP-9001 (AAVrh74.MHCK7.micro-dystrophin) is Sareptas investigational gene transfer therapy for the treatment of Duchenne muscular dystrophy.

Among other items, OTAT has requested that Sarepta utilize an additional potency assay for release of SRP-9001 commercial process material prior to dosing in a clinical study. Sarepta has several existing assays and data that it believes could be employed in response to OTATs request. However, additional dialogue with the Agency is required to determine the acceptability of the potency assay approach.

We look forward to working with OTAT to potentially satisfy their requests and to obtain clarity on the timing of the commencement of our commercial supply study. We will provide further updates as we are able, said Doug Ingram, president and chief executive officer, Sarepta Therapeutics. Every day, thousands of children degenerate from the irreversible damage caused by Duchenne muscular dystrophy. It is for that reason that we will work relentlessly with the Division to satisfy any requests of OTAT and continue the advancement of a potentially transformative therapy for these patients.

About SRP-9001 (AAVrh74.MHCK7.micro-dystrophin)SRP-9001 is an investigational gene transfer therapy intended to deliver the micro-dystrophin-encoding gene to muscle tissue for the targeted production of the micro-dystrophin protein. Sarepta is responsible for global development and manufacturing for SRP-9001 and plans to commercialize SRP-9001 in the United States. In December 2019, the Company announced a licensing agreement granting Roche the exclusive right to launch and commercialize SRP-9001 outside the United States. Sarepta has exclusive rights to the micro-dystrophin gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Childrens Hospital.

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

Sarepta Forward-Looking Statements

This press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding Sareptas belief that its existing assays and data could be employed in response to OTATs request; the acceptability of Sareptas potency assay approach by the FDA; our plan to work with OTAT to potentially satisfy their requests and to obtain clarity on the timing of the commencement of our commercial supply study; and the potential of SRP-9001 to be a transformative therapy for DMD patients.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sareptas control. Known risk factors include, among others: delays in the commencement of Sareptas next clinical study for SRP-9001 could delay, prevent or limit our ability to gain regulatory approval for SRP-9001; any inability to complete successfully clinical development could result in additional costs to Sarepta or impair Sareptas ability to generate revenues from product sales, regulatory and commercialization milestones and royalties; SRP-9001 may not result in a viable treatment suitable for commercialization due to a variety of reasons, including the results of future research may not be consistent with past positive results or may fail to meet regulatory approval requirements for the safety and efficacy of product candidates; Sarepta may not be able to execute on its business plans and goals, including meeting its expected or planned regulatory milestones and timelines, clinical development plans, and bringing its product candidates to market, due to a variety of reasons, many of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates and the COVID-19 pandemic; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2019, and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by Sarepta which you are encouraged to review.

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

Internet Posting of Information

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

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

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

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

Continued here:
Sarepta Therapeutics Provides Program Update for SRP-9001, its Investigational Gene Therapy for the Treatment of Duchenne Muscular Dystrophy -...

PLEASANTON, Calif., Sept. 15, 2020 (GLOBE NEWSWIRE) --10x Genomics (Nasdaq: TXG) today announced it has begun shipping its Chromium Single Cell Multiome ATAC + Gene Expression solution to customers, marking the first commercial release of a product capable of simultaneously profiling the epigenome and transcriptome from the same single cell. This multi-omic approach provides customers with the ability to link a cells epigenetic program to its transcriptional output, enabling a better understanding of cell functionality and bypassing the need to infer relationships through computer simulations.

This is one of our most ambitious undertakings at the company, said Ben Hindson, co-founder and Chief Scientific Officer of 10x Genomics. By introducing the first solution that captures ATAC and gene expression simultaneously, researchers can gain even more clarity by combining two already powerful methods to profile biological systems at single cell resolution simultaneously for the first time.

The new solution builds on an array of new products launched by the company this year for both its Chromium platform for single cell analysis as well as its Visium platform for spatial genomics. Early customers already working with Chromium Single Cell Multiome ATAC + Gene Expression include Stanford University School of Medicine, Icahn School of Medicine at Mt. Sinai and Spains Centro Nacional de Anlisis Genmico.

My lab is interested in understanding why some immune cell types fail to fight the cancer, said Dr. Ansuman Satpathy, Assistant Professor of Pathology, Stanford University School of Medicine. We plan to use 10x Genomics' new assay to understand the epigenetic and transcriptional regulation of immune cell dysfunction directly in patient samples, and to use this information to precisely engineer more effective immunotherapies in the future.

Until now, we have relied on computational prediction to match a cell's epigenome to a single-cell gene expression profile, said Dr. Holger Heyn, leader of the single cell genomics team at Spains Centro Nacional de Anlisis Genmico that is working on delineating the dynamics underlying B-cell differentiation and activation. 10x Genomics new multiome assay will allow us to directly measure what before could only be predicted, and offers a new gold standard that will confirm how accurate these predictions had been.

"With this new technology, we can better understand the mechanisms affected by the non-coding risk genetic variation across a wide range of neuropsychiatric diseases, including Alzheimers, Parkinsons, Schizophrenia, bipolar disorder and major depression, along with different severity of neuropathology and clinical symptomatology," added Dr. Panagiotis Roussos, Associate Professor of Genetics and Genomics Sciences, Icahn School of Medicine at Mount Sinai.

By using Chromium Single Cell Multiome ATAC + Gene Expression, researchers can:

Chromium Single Cell Multiome ATAC + Gene Expression is shipping to customers. To learn more, visit https://www.10xgenomics.com/products/single-cell-multiome-atac-plus-gene-expression.

About 10x Genomics10x Genomics is a life science technology company building products to interrogate, understand and master biology to advance human health. The companys integrated solutions include instruments, consumables and software for analyzing biological systems at a resolution and scale that matches the complexity of biology. 10x Genomics products have been adopted by researchers around the world including 97 of the top 100 global research institutions and 19 of the top 20 global pharmaceutical companies, and have been cited in over 1,500 research papers on discoveries ranging from oncology to immunology and neuroscience. The companys patent portfolio comprises more than 775 issued patents and patent applications.

Forward Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 as contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements generally can be identified by the use of forward-looking terminology such as may, will, should, expect, plan, anticipate, could, intend, target, project contemplate, believe, estimate, predict, potential or continue or the negatives of these terms or variations of them or similar terminology. These forward-looking statements include statements regarding 10x Genomics, Inc.s partnership activities, which involve risks and uncertainties that could cause 10x Genomics, Inc.s actual results to differ materially from the anticipated results and expectations expressed in these forward-looking statements. These statements are based on managements current expectations, forecasts, beliefs, assumptions and information currently available to management, and actual outcomes and results could differ materially from these statements due to a number of factors. These and additional risks and uncertainties that could affect 10x Genomics, Inc.s financial and operating results and cause actual results to differ materially from those indicated by the forward-looking statements made in this press release include those discussed under the captions "Risk Factors" and "Management's Discussion and Analysis of Financial Condition and Results of Operations" and elsewhere in the documents 10x Genomics, Inc. files with the Securities and Exchange Commission from time to time. The forward-looking statements in this press release are based on information available to 10x Genomics, Inc. as of the date hereof, and 10x Genomics, Inc. disclaims any obligation to update any forward-looking statements provided to reflect any change in its expectations or any change in events, conditions, or circumstances on which any such statement is based, except as required by law. These forward-looking statements should not be relied upon as representing 10x Genomics, Inc.s views as of any date subsequent to the date of this press release.

Disclosure Information10x Genomics uses filings with the Securities and Exchange Commission, its website (www.10xgenomics.com), press releases, public conference calls, public webcasts and its social media accounts as means of disclosing material non-public information and for complying with its disclosure obligations under Regulation FD.

ContactsMedia:media@10xgenomics.comInvestors:investors@10xgenomics.com

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10x Genomics First to Market With Product to Simultaneously Capture Epigenome and TranscriptomeChromium Single Cell Multiome ATAC + Gene Expression...

LONDON The international commission convened in the aftermath of Chinese scientist He Jiankuis shock announcement of the birth of gene edited twins has set a possible course to approval of heritable gene editing, but said the technique is far from ready for use.

At this time, it is not possible to specify how to move from research to clinical application because it is not possible to make precise edits, or avoid introducing off-target effects, the committee said.

No clinical use should be considered until it is clear it can be done precisely. There are a lot of gaps at the moment, said Kay Davies, commission co-chair and professor of genetics at Oxford University, speaking at the launch of the report.

Should they ever be used, it is vitally important that these technologies are used for medically justified interventions based on rigorous understanding of how the pathogenic variant leads to disease, Davies said.

If and when heritable human genome editing is proved reliable, initial applications should be limited to the prevention of serious monogenic diseases, such as cystic fibrosis, thalassemia, sickle cell anemia and Tay-Sachs disease, but only in cases where even with in vitro fertilization and preimplantation screening of embryos, couples would have no chance of having a biologically related child that was not affected by the condition.

As the report notes, instances where both prospective parents are homozygous for a disease gene are very rare. Even for a dominant disorder that can be inherited from a single defective gene, it would be rare for one parent to be homozygous. Commission member Michele Ramsay, of the University of the Witwatersrand, South Africa, said fewer than 20 families worldwide are likely to meet the criteria.

Thats why we need international cooperation, so it is transparent and open, and data can be pooled, Ramsay said. No floodgates are going to be opened for the initial uses we recommend.

The International Commission on the Clinical Use of Human Germline Gene Editing, set up by the U.K. Royal Society and the U.S. National Academies of Science and of Medicine, involves 18 expert members from 10 countries. They spent a year reviewing the scientific literature on CRISPR and other gene editing tools, consulting peer and patients groups and meeting the public.

For the prevention of serious monogenic disease, the commission has defined a responsible clinical translation pathway, from rigorous preclinical research that determines whether and how editing can be performed efficiently and with high accuracy, to clinical application, said Richard Lifton, co-chair of the commission and president of Rockefeller University.

Key technical barriers are assessing if an edit will be corrective and demonstrating the intended edit is present in all cells. These criteria for safe and effective use have not been met yet, said commission member Haoyi Wang, of the Chinese Academy of Sciences. The report sets out the progress of research needed to show editing is effective, and [can be done] with high specificity and accurate on target charges, without causing off-target effects or mosaicism, Wang said.

No one should be attempting to follow Hes example as things stand, the commission said. All countries in which human gene editing is being researched should put in place regulation to oversee progress toward potential clinical uses, and to prevent and sanction unapproved use.

There is great concern about the potential for rogue scientists embarking on heritable gene editing on their own, Lifton said. Ultimately, regulation will be at the countrywide level, but weve got to ensure the conditions are met to ensure proper regulatory oversight. There must be a mechanism for case by case evaluation and staged rollout of the technology, he said.

More research needed

To back those national regulations, an international science advisory panel should be established to continuously follow progress, assess if preclinical requirements have been met, review data on clinical outcomes from any regulated uses of human germline editing, and advise on risks and benefits of other potential applications.

More research is needed into the technology of genome editing in human embryos, to ensure that precise changes can be made without undesired off-target effects, said Davies. International cooperation and open discussion of all aspects of genome editing will be essential.

In addition to a scientific panel to follow the science, the commission also calls for a hotline to be set up, through which researchers could raise concerns about any inappropriate use of germline editing. I would emphasize the importance of a whistleblowing mechanism, said Davies. It is suggested this could be modeled on the World Anti-Doping Agency, which polices the use of prohibited substances in sports.

The commission stresses that it was solely concerned with assessing the science and defining the specific criteria and standards required before clinical use of germline editing is considered.

A separate committee set up by the World Health Organization and co-chaired by Margaret Hamburg, former head of the U.S. FDA, is looking at ethical issues and developing governance mechanisms for both heritable and somatic gene editing. The WHO committee is expected to publish its guidance later this year.

In December 2019, He was sentenced to three years in prison and fined $430,000 for illegally carrying out the human gene editing that led to the birth of the twin girls and of another baby, with heritable changes to their genomes.

As to how far in the future approval for germline gene editing might be, Wang said the technology is moving fast. Its a bit difficult to predict, but Im quite optimistic it will become more precise. Advances also will be needed in single cell genome sequencing to ensure there are no off-target effects, he said.

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Commission urges international cooperation, continuing research in gene editing report - BioWorld Online

Scientists from UBCs faculty of medicine and the Institute of Molecular Biology of the Austrian Academy of Sciences (IMBA) have discovered that the gene, known as JAGN1, plays an important role in antibody production and the bodys ability to mount a defense against pathogens, including viruses.

The findings were published online today in the Journal of Experimental Medicine.

Dr. Josef Penninger

Antibodies play a fundamental role in medicine, and antibody-mediated immune response is the ultimate target in the quest for a vaccine to defeat the current pandemic, says the studys senior author Dr. Josef Penninger, a professor in the department of medical genetics and director of the Life Sciences Institute at UBC and a researcher at IMBA.

As part of their investigation, Dr. Penningers research groups at UBC and IMBA shed light on the role of JAGN1 in relation to B cells, which are white blood cells that can develop into plasma cells when they recognize foreign substances, such as chemicals, bacteria, viruses and pollen. In their plasma cell form, B cells can produce thousands of antibodies per second that target a specific intruder. This production occurs at a location within the cell known as the endoplasmic reticulum.

When we knocked out JAGN1 in B cells of mice, we were able to measure a drastic reduction in the number of antibodies, says the studys first author Dr. Astrid Hagelkruys, a senior research associate at IMBA.

The researchers also found that the altered sugar molecules, which coat antibodies, facilitate an antibodys ability to bind to other immune cells, thereby strengthening the bodys defensive reaction.

JAGN1 seems to influence the antibody factories in the cells, says Dr. Penninger. To our surprise, this change in the sugar structure also leads to a better ability of the antibodies to bind to other immune cells and strengthens the defense reaction.

The scientists were able to demonstrate this mechanism in human samples.

Rare genetic defects occur in only a handful of people, but they can sometimes help us decipher basic principles of biology, adds Dr. Penninger. In this case, we were able to prove that a certain gene affects the endoplasmic reticulum and is therefore essential for the mass production of antibodies.

The gene JAGN1 had been previously identified as a player in the bodys immune system by the Penninger lab in collaboration with the Klein lab at Ludwig Maximilian University in Munich among patients with severe congenital neutropenia (SCN)a disease caused by a mutation in the JAGN1 gene. Patients with SCN have abnormally low levels of white blood cells called neutrophils, and suffer from serious infections because their immune systems cannot effectively kill off bacterial or fungal invaders.

More here:
Scientists uncover essential role of one gene in antibody production - UBC Faculty of Medicine

Eli Lilly said it planned to discuss with regulators the possible emergency use of baricitinib for hospitalized patients. Other news is about early research on an antibody that might neutralize COVID and how the virus controls the brain, as well.

AP:Anti-Inflammatory Drug May Shorten COVID-19 Recovery TimeA drug company says that adding an anti-inflammatory medicine to a drug already widely used for hospitalized COVID-19 patients shortens their time to recovery by an additional day. Eli Lilly announced the results Monday from a 1,000-person study sponsored by the U.S. National Institute of Allergy and Infectious Diseases. The study tested baricitinib, a pill that Indianapolis-based Lilly already sells as Olumiant to treat rheumatoid arthritis. (Marchione, 9/14)

The Hill:Drugmaker Says Anti-Inflamatory Medicine May Shorten COVID-19 Recovery TimeThe use of Baricitinib, arheumatoidarthritis drug from Eli Lilly, led to a one-day reduction in recovery time for patients when combined with Remdesivir compared to patients who only took Remdesivir, according to a trial. The finding was statistically significant, Eli Lilly said in a statement. The company did not release the full results of the study but stated the National Institute of Allergy and Infectious Diseases (NIAID) is expected to publish full results in peer-review studies and that additional analyses are ongoing to understand clinical outcome data, including safety and morbidity data. (9/14)

In other scientific developments

Fox News:University Of Pittsburgh Scientists Discover Antibody That 'neutralizes' Virus That Causes CoronavirusScientists at the University of Pittsburgh School of Medicine have isolated the smallest biological molecule that completely and specifically neutralizes SARS-CoV-2, the virus that causes the novel coronavirus. The antibody component is 10 times smaller than a full-sized antibody, and has been used to create the drug Ab8, shared in the report published by the researchers in the journal Cell on Monday. The drug is seen as a potential preventative against SARS-CoV-2. (Deabler, 9/14)

Fox News:Coronavirus Can 'Hijack' Brain Cells To Replicate Itself, Yale Researchers DiscoverThe coronavirus can affect the brain and hijack brain cells to replicate itself, Yale University researchers have discovered. A new study from Yale University, on BioRXiv, which is awaiting peer review, found that the brain is another organ susceptible to an attack by the novel coronavirus. (McGorry, 9/14)

Stat:23andMe Research Finds Possible Link Between Blood Type And Covid-19A forthcoming study from genetic testing giant 23andMe shows that a persons genetic code could be connected to how likely they are to catch Covid-19 and how severely they could experience the disease if they catch it. Its an important confirmation of earlier work on the subject. People whose blood group is O seemed to test positive for Covid-19 less often than expected when compared to people with any other blood group, according to 23andMes data; people who tested positive and had a specific variant of another gene also seemed to be more likely to have serious respiratory symptoms. (Sheridan, 9/14)

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Drug Company Touts Anti-Inflammatory Drug's Role In Shortening COVID Recovery - Kaiser Health News

Myotonic dystrophy type I (DM1) is the most common type of adult-onset muscular dystrophy. DM1 is caused by mutations in the DMPK gene. A normal DMPK gene has 3 to 37 repetitions of the CTG sequence, while in DM1, there are hundreds to thousands of repetitions of this sequence. When a DMPK gene with too many CTG repeats is transcribed, the resulting RNA is too long. This abnormally long RNA is toxic to cells, and those affected experience progressive muscle wasting and weakness.

CRISPR-Cas9 is a technique increasingly used in efforts to correct the genetic defects that cause a variety of diseases. Now a research team from the University of California, San Diego (UCSD), School of Medicine, reports they redirected the technique to modify RNA in a method they call RNA-targeting Cas9 (RCas9), to eliminate the toxic RNA and almost fully reverse symptoms in a mouse model of myotonic dystrophy.

Their findings, The sustained expression of Cas9 targeting toxic RNAs reverses disease phenotypes in mouse models of myotonic dystrophy type 1, was published in Nature Biomedical Engineering and led by Gene Yeo, PhD, professor of cellular and molecular medicine at UCSD School of Medicine.

Myotonic dystrophy is part of a group of inherited disorders called muscular dystrophies. There are two major types of myotonic dystrophy: type 1 and type 2. The muscle weakness associated with type 1 particularly affects muscles farthest from the center of the body, such as those of the lower legs, hands, neck, and face. Muscle weakness in type 2 primarily involves muscles close to the center of the body, such as those of the neck, shoulders, elbows, and hips. The two types of myotonic dystrophy are caused by mutations in different genes.

Many other severe neuromuscular diseases, such as Huntingtons and ALS, are also caused by similar RNA buildup, explained Yeo. There are no cures for these diseases. Yeo led the study with collaborators at Locanabio and the University of Florida.

CRISPR-Cas9 works by directing Cas9 to cut a specific target gene, allowing researchers to inactivate or replace the gene. However, the Cas9 in the RCas9 method is guided to an RNA molecule instead of DNA. In a previous study, Yeo and his team established RCas9 as a means to track RNA in living cells in a programmable manner without genetically encoded tags. In a 2017 study, in lab models and patient-derived cells, the researchers used RCas9 to eliminate 95% of the abnormal RNA linked to myotonic dystrophy type 1 and type 2, one type of ALS and Huntingtons disease.

In the current study, the method goes further, by reversing myotonic dystrophy type 1 in a mouse model of the disease. Toxic RNAs expressed from such repetitive sequences can be eliminated using CRISPR-mediated RNA targeting, yet evidence of its in vivo efficacy and durability is lacking, noted the researchers. Here, using adult and neonatal mouse models of DM1, we show that intramuscular or systemic injections of adeno-associated virus (AAV) vectors encoding nuclease-dead Cas9 and a single-guide RNA targeting CUG repeats results in the expression of the RNA-targeting Cas9 for up to three months, redistribution of the RNA-splicing protein muscleblind-like splicing regulator 1, elimination of foci of toxic RNA, reversal of splicing biomarkers and amelioration of myotonia.

The researchers packaged RCas9 in a non-infectious virus. They then gave the mice a single dose of the therapy or a placebo. RCas9 reduced the abnormal RNA repeats by more than 50%, varying a bit depending on the tissue, and the treated myotonic dystrophy mice became indistinguishable from healthy mice.

To prevent the potential of the RCas9 proteins, developing an immune reaction in the mice, the researchers tried suppressing the mices immune systems briefly during treatment. As a result, they were surprised to see that they successfully prevented immune reaction and clearance. The researchers did not see signs of muscle damage, but found an increase in the activity of genes involved in new muscle formation.

Yeo believes the findings will open a new avenue of understanding and lead the way for treating other genetic diseases. This opens up the floodgates to start testing RNA-targeting CRISPR-Cas9 as a potential approach to treat other human genetic diseasesthere are at least 20 caused by buildup of repetitive RNAs, Yeo added.

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Muscular Dystrophy Condition in Mice Reversed by RNA-Targeting Cas9 - Genetic Engineering & Biotechnology News

MEDIA ADVISORY

FOR IMMEDIATE RELEASE: Nature Communications: Published Monday, September 14, 2020

Newswise Corresponding Author:Yasmin Hurd, PhD, Director of The Addiction Institute of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, and other coauthors.

Bottom Line:Herion-addicted individuals have alterations in the expression a gene called FYN - a gene known to regulate the production of Tau, a protein that is highly elevated and implicated in neurocognitive disorders like Alzheimers disease. The study emphasizes that opioid use can affect the brain in a way that might increase vulnerability of neural systems that trigger neurodegeneration later in life; however, since these changes are epigenetic (alterations in gene function that are influenced by environmental factors and not alterations of the DNA itself), they are reversible and medications that have already been developed to target FYN for neurodegenerative disorders may be studied as a novel treatment for opioid addiction.

Results:Interestingly, findings were consistent across human, animal and cell models. Through post-mortem analysis of the brains of human heroin users, the team found that, specifically in neurons, the most significantly impaired epigenetic region is related to a gene called FYN. Essentially, heroin opened up the DNA at the FYN gene, which encodes a protein called tyrosine kinase FYN, that is strongly linked to synaptic plasticity and which directly results in production of Tau. Too much Tau in the brain is associated with neurodegenerative diseases. They observed that expression and activity of tyrosine kinase FYN was also induced in rats trained to self-administer heroin and also in primary striatal neurons treated with chronic morphine in vitro. Additionally, they demonstrated that inhibition of the FYN kinase (either via pharmacological means or through genetic manipulation) reduces heroin-seeking and heroin-taking behaviors.

Why the Research Is Interesting:The findings will increase awareness about the potential impact of heroin to alter neural systems related to neurodegenerative disorders. The findings also identify FYN inhibitors as a novel therapeutic treatment for heroin use disorders.

Who: Human brains from a cohort of subjects who succumbed to heroin overdose and normal controls, translational animal model of rats trained to self-administer heroin, and primary striatal neurons treated with chronic morphine in vitro.

When: Adult animals were exposed to heroin and their brains studied.

What:They performed unbiased, cell-type-specific, genome-wide profiling of chromatin accessibility, providing insights into epigenetic regulation directly in the brains of heroin-addicted individuals. To assess the causal relationship between heroin use and FYN pathology, they studied the brains of rats trained to self-administer heroin and they hit primary striatal neurons with chronic morphine in petri dishes to examine the effect at the individual cellular level.

Study Conclusions:By scanning the entire genome of heroin users to identify whether disturbances in how genes are turned on or off exist, Mount Sinai researchers found that heroin opened up the DNA at the FYN gene. The FYN gene is known to regulate the production of Tau, a protein implicated in neurodegenerative disorder like Alzheimers disease, meaning that heroin may put users at an increased risk of neurodegenerative disease later in life. Importantly, these novel findings suggest that FYN inhibitors (which have already been developed and are being assessed for use in Alzheimers disease) may be promising therapeutic tools for heroin-use disorder.

Paper Title: Chromatin accessibility mapping of the striatum identifies tyrosine kinase FYN as a therapeutic target for heroin use disorder

Said Mount Sinai's Dr. Yasmin Hurd of the research: Drug overdoses due to opioid abuse remain at epidemic levels and continue to rise precipitously during the current pandemic, with novel treatments desperately needed. Direct molecular insights into the heroin-addicted human brain are critical to guide future therapies. Our new study findings clearly open up new lines of treatment opportunities for opioid use disorder, which could benefit and potentially save the lives of so many.

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People with Heroin Addiction Have Unique Molecular Alterations to The Brain That Resemble Brain Disturbances Seen in Neurodegenerative Disorders Like...

More than 1 million Americans are diagnosed with a chronic brain disorder each year, yet effective treatments for most complex brain disorders are inadequate or even nonexistent.

A major new research effort at the McGovern Institute for Brain Research at MIT aims to change how we treat brain disorders by developing innovative molecular tools that precisely target dysfunctional genetic, molecular, and circuit pathways.

The K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience was established at MIT through a $28 million gift from philanthropist Lisa Yang and MIT alumnus Hock Tan 75. Yang is a former investment banker who has devoted much of her time to advocacy for individuals with disabilities and autism spectrum disorders. Tan is president and CEO of Broadcom, a global technology infrastructure company.This latest gift brings Yang and Tans total philanthropy to MIT to more than $72 million.

In the best MIT spirit, Lisa and Hock have always focused their generosity on insights that lead to real impact," says MIT President L. Rafael Reif. Scientifically, we stand at a moment when the tools and insights to make progress against major brain disorders are finally within reach. By accelerating the development of promising treatments, the new center opens the door to a hopeful new future for all those who suffer from these disorders and those who love them. I am deeply grateful to Lisa and Hock for making MIT the home of this pivotal research.

Engineering with precision

Research at the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience will initially focus on three major lines of investigation: genetic engineering using CRISPR tools, delivery of genetic and molecular cargo across the blood-brain barrier, and the translation of basic research into the clinical setting. The center will serve as a hub for researchers with backgrounds ranging from biological engineering and genetics to computer science and medicine.

Developing the next generation of molecular therapeutics demands collaboration among researchers with diverse backgrounds, says Robert Desimone, McGovern Institute director and the Doris and Don Berkey Professor of Neuroscience at MIT. I am confident that the multidisciplinary expertise convened by this center will revolutionize how we improve our health and fight disease in the coming decade. Although our initial focus will be on the brain and its relationship to the body, many of the new therapies could have other health applications.

There are an estimated 19,000 to 22,000 genes in the human genome and a third of those genes are active in the brain the highest proportion of genes expressed in any part of the body. Variations in genetic code have been linked to many complex brain disorders, including depression, Parkinsons, and autism. Emerging genetic technologies, such as the CRISPR gene editing platform pioneered by McGovern Investigator Feng Zhang, hold great potential in both targeting and fixing these errant genes. But the safe and effective delivery of this genetic cargo to the brain remains a challenge.

Researchers within the new Yang-Tan Center will improve and fine-tune CRISPR gene therapies and develop innovative ways of delivering gene therapy cargo into the brain and other organs. In addition, the center will leverage newly developed single-cell analysis technologies that are revealing cellular targets for modulating brain functions with unprecedented precision, opening the door for noninvasive neuromodulation as well as the development of medicines. The center will also focus on developing novel engineering approaches to delivering small molecules and proteins from the bloodstream into the brain. Desimone will direct the center and some of the initial research initiatives will be led by associate professor of materials science and engineering Polina Anikeeva; Ed Boyden, the Y. Eva Tan Professor in Neurotechnology at MIT; Guoping Feng, the James W. (1963) and Patricia T. Poitras Professor of Brain and Cognitive Sciences at MIT; and Feng Zhang, James and Patricia Poitras Professor of Neuroscience at MIT.

Building a research hub

My goal in creating this center is to cement the Cambridge and Boston region as the global epicenter of next-generation therapeutics research. The novel ideas I have seen undertaken at MITs McGovern Institute and Broad Institute of MIT and Harvard leave no doubt in my mind that major therapeutic breakthroughs for mental illness, neurodegenerative disease, autism, and epilepsy are just around the corner, says Yang.

Center funding will also be earmarked to create the Y. Eva Tan Fellows program, named for Tan and Yangs daughter Eva, which will support fellowships for young neuroscientists and engineers eager to design revolutionary treatments for human diseases.

We want to build a strong pipeline for tomorrows scientists and neuroengineers, explains Hock Tan. We depend on the next generation of bright young minds to help improve the lives of people suffering from chronic illnesses, and I can think of no better place to provide the very best education and training than MIT.

The molecular therapeutics center is the second research center established by Yang and Tan at MIT. In 2017, they launched the Hock E. Tan and K. Lisa Yang Center for Autism Research, and, two years later, they created a sister center at Harvard Medical School, with the unique strengths of each institution converging toward a shared goal: understanding the basic biology of autism and how genetic and environmental influences converge to give rise to the condition, then translating those insights into novel treatment approaches.

All tools developed at the molecular therapeutics center will be shared globally with academic and clinical researchers with the goal of bringing one or more novel molecular tools to human clinical trials by 2025.

We are hopeful that our centers, located in the heart of the Cambridge-Boston biotech ecosystem, will spur further innovation and fuel critical new insights to our understanding of health and disease, says Yang.

The rest is here:
New molecular therapeutics center established at MIT's McGovern Institute - MIT News

This week, Prime Minister Scott Morrison announced the findings of the Productivity Commission report into mental health. It estimated that the economic cost of mental ill-health and suicide in Australia was up to $70 billion a year, and that disability and early death caused byit cost a further $151 billion a year.

If there has ever been time for a paradigm shift in the way we conceptualise mental health and mental illness, it must be now. As we battle with a global rising tide of mental illness, there should be recognition that radically new approaches are needed to treat these diseases.

Part of the reason that the incidence of mental illness is increasing in the community is because we're now more aware of it, and also because there's far less stigma attached to it than in the past.

Butdespite more people seeking help, there are also more people, globally, committing suicide, with an alarming increase over the past three years after some stability in these figures since the 1970s. And that was before COVID-19 brought its isolation, unemployment, anxiety and illness to our world.

In the same way we now routinely offer personalised precision medicine for cancer treatment with the genetic makeup of an individuals tumour determining treatment rather than broad-brush diagnoses such as lung cancer or breast cancer it'stime to look at psychiatric illness in the same way.

Disorders such as schizophrenia and depression are not single diseases, but labels used to cluster symptoms.

In the case of depression, these symptoms include constant sadness, irritability, hopelessness, decreased energy, and sleeping problems. Schizophrenia has numerous disabling symptoms, including delusions, hallucinations, memory and thinking problems, and depression.

Both these conditions have a strong link with family heredity. Depression has a genetic link of approximately 40-70% ,and schizophrenia a genetic link of between 50-80%. The problem is that these disorders, like others such as bipolar disorder and autism, have multiple genes that are in play, which makes fanciful the approach of targeting a single gene with a drug or therapy and hoping to treat everybody.

But what if we had a similar program to that for cancers, which also have multiple genetic causes, dedicated to mental health issues?

Fifty years ago, only one in three people diagnosed with the blood cancer leukaemia would survive a year with the disease. Now, that statistic has been flipped, with at least half surviving up to 10.

The changes are even more remarkable for other cancers, but it was a long slog determining the genes associated with each disease, and developing treatments that targeted each genetic mutation. Then there was the enormous task of being able to determine that genetic mutation, and tailoring treatment for every person diagnosed with cancer.

It was predicted, decades ago, that such an approach might work, but it would be enormously costly. And yet here we are with personalised medicine one of the backbones of oncology.

Of course, psychiatric illness is harder to tackle than cancer. We cant just sample bits of peoples brains to look for genetic mutations. Instead we have to rely on family histories, brain imaging and electrical recordings, blood assays, and the use of animal models to link a disease to a gene(s), and then find a drug that targets that gene.

Melbourne is one of the few places in the world that has these sorts of programs. In 2018, a global study led by University of Melbournes Professor Sam Berkovic examined the DNA of more than 45,000 people with epilepsy, leading to the discovery of 11 genes associated with the disorder, paving the way for drugs that could benefit millions of patients who didn't respond to existing treatments.

At Monash, we have similar programs looking at the genes and proteins that cause schizophrenia and other psychotic disorders, with a view to individualising treatments for people with different types of the disease.

We're amida mental illness epidemic, and quicker recognition and providing more treatment for those in need is extremely important. But we need a paradigm shift in the way we tackle mental illness, in the same way those leukaemia researchers did 40 years ago.

Professor Suresh Sundramis a speaker at the From the Front Line: Rethinking Mental Health webinar, at 11.30am on Wednesday, 25 November. You can register for the event here.

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Now is the time for a paradigm shift in how we treat mental ill health Monash Lens - Monash Lens

DetailsCategory: More NewsPublished on Wednesday, 16 September 2020 10:43Hits: 105

NEW YORK, NY, USA I September 15, 2020 I As part of a two-day virtual Investor Day, Pfizer Inc. (NYSE: PFE) provided an extensive overview of pipeline advances and shared updates on the Companys efforts to battle the COVID-19 pandemic on multiple fronts, including new data on the BNT162b2 vaccine candidate being developed in collaboration with BioNTech SE. The pipeline updates contribute to the Companys expectation of at least a 6% revenue CAGR over the next five years, as well as delivery of longer-term topline growth beyond that period.

Pfizers goal of delivering up to 25 breakthroughs to patients by the year 2025 has 38 such opportunities to draw from as of today, including the companys 20-valent pneumococcal conjugate vaccine candidate (20vPnC). On a non-risk adjusted basis, these opportunities collectively represent more than $15 billion (excluding 20vPnC) in potential incremental revenue for Pfizer from 2020 to 2025, as well as aggregate peak annual sales potential of $35 billion to $40 billion (including 20vPnC). If successful, the Companys COVID-19 programs would be incremental to these estimates.

Pfizers purpose Breakthroughs that change patients lives has never been more relevant, and our R&D pipeline has never been more dynamic, said Dr. Albert Bourla, Pfizer Chairman and CEO. I am proud of the truly transformational science that our research and clinical teams are bringing to the fight against disease, as well as the unprecedented speed with which we are advancing our clinical programs in the battle against COVID-19. In the coming months and years, I look forward to the new Pfizer continuing to demonstrate the agility and innovative spirit of a biotech combined with the scale of Big Pharma. With the depth and breadth of our current portfolio, the tremendous potential of our pipeline and scientific engine, and the power of our culture of innovation, we are poised to continue delivering meaningful value to patients by addressing some of the worlds most difficult health challenges.

UPDATES ON COVID-19 DEVELOPMENT PROGRAMS

Pfizer announced several key advances in its efforts to protect humankind from the COVID-19 pandemic and prepare the pharmaceutical industry to better respond to future global health crises.

BNT162 mRNA-based Vaccine Program

Pfizer and BioNTech shared several updates from their BNT162 mRNA-based vaccine program against SARS-CoV-2, the virus that causes COVID-19 disease, including:

Protease Inhibitor Program

The company announced the initiation of its Phase 1b clinical trial to evaluate the safety of a novel investigational therapeutic for COVID-19, PF-07304814. Of note,

THERAPEUTIC AREAS OF FOCUS

Pfizer shared significant research advances across its various therapeutic areas including candidates with blockbuster potential expected to launch by 2025.

Vaccines

In addition to the COVID-19 vaccine program, Pfizer aims to deliver five innovative vaccines by 2025, subject to clinical success and regulatory approval. Updates on these late-stage clinical development programs include:

Rare Disease

Pfizers Rare Disease late-stage pipeline currently includes three gene therapy programs that, if successful, are expected to gain regulatory approval by the end of 2023, with an additional pipeline of 10 preclinical initiatives that are at various stages of maturity. Key updates include:

Oncology

Pfizers Oncology pipeline has the potential to deliver up to 14 approvals expected by the end of 2025 and the potential for 24 new molecular entities in the clinic by the end of 2021. Key updates included, for the first time, early-stage opportunities obtained from the 2019 acquisition of Array BioPharma:

Inflammation and Immunology

The Inflammation & Immunology pipeline is focused on patients with autoimmune and chronic inflammatory diseases across rheumatology, gastroenterology and dermatology, with five distinct immuno-kinases, in oral and topical formulations, studied for potential treatment of 10 diseases, and three additional novel biologics in Phase 2 studies. Key updates included:

Internal Medicine

The Internal Medicine pipeline addresses the increasing global burden of cardiometabolic disease, with nine investigational medicines in active clinical studies and additional therapies in the pre-clinical pipeline. Key updates included:

To access a replay of the webcast, including audio, video and presentation slides, visit our web site at http://www.pfizer.com/investors.

About Pfizer: Breakthroughs That Change Patients Lives

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at http://www.Pfizer.com. In addition, to learn more, please visit us on http://www.Pfizer.com and follow us on Twitter at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.

SOURCE: Pfizer

Excerpt from:
Pfizer Investor Day Features Significant Number of Pipeline Advances for COVID-19 Programs and Across Numerous Therapeutic Areas | More News | News...

In the United States, cardiovascular deaths that were not directly due to COVID-19 surged early in the pandemic. The postponement of procedures, the extra strain on services, and patients avoidance of hospitals may partly explain the increase.

About one-third of the 225,530 excess deaths in the U.S. during the first months of the pandemic were not directly due to COVID-19, according to a recent study.

Despite this additional death toll, other research showed that the number of people admitted to the hospital with cardiovascular conditions fell sharply in March 2020, coinciding with the rise in COVID-19 cases.

Hospital visits for heart attacks and other cardiac conditions declined markedly during the pandemic, fueling physicians concerns that people with acute conditions may be staying at home due to fear of exposure to COVID-19, says Dr. Rishi K. Wadhera, a cardiologist at the Beth Israel Deaconess Medical Center (BIDMC) in Boston, MA.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

New research adds to these concerns. According to the study, which Dr. Wadhera led, cardiovascular deaths unrelated to COVID-19 increased in New York State, New Jersey, Michigan, and Illinois during the first wave of the pandemic relative to cardiovascular deaths in the same period of 2019.

In New York City, which the first wave hit particularly hard, deaths from ischemic heart disease (which results from narrowed cardiac arteries) increased by 139%, and deaths from hypertensive disease (due to high blood pressure) increased by 164%.

These data are particularly relevant today, as we find ourselves in the midst of a surge in COVID-19 cases that looks to be exceeding what we experienced last spring, says senior author Robert Yeh, director of the Smith Center for Outcomes Research at BIDMC.

Ensuring that patients with cardiovascular disease continue to receive necessary care during our public health response to the pandemic will be of paramount importance, he adds.

The analysis appears in the Journal of the American College of Cardiology.

The researchers drew on data from the National Center for Health Statistics to compare cardiovascular death rates at the start of the pandemic (from March 18, 2020, to June 2, 2020) with those during the preceding 11 weeks.

To account for seasonal trends, they then compared this figure with the change in cardiovascular death rates over the same period in 2019.

Overall, the rate of deaths due to ischemic heart disease increased by 11% over this period in 2020 compared with the previous year. The rate of deaths resulting from hypertensive disease increased by 17%.

There was no increase in death rates from heart failure, cerebrovascular disease (such as strokes), or other circulatory diseases.

The surge in cardiac death rates was concentrated in New York State, New Jersey, Michigan, and Illinois, which were among the states most affected by COVID-19 during the first wave of the pandemic.

One exception was Massachusetts, which did not see increases in cardiac death rates, despite being an epicenter of COVID-19 cases.

The researchers speculate that people who experienced acute cardiac symptoms may have avoided medical care because they were worried about contracting the virus in the hospital. As a result, more people died at home without receiving the necessary treatment.

The study authors note that the incidence of cardiac arrests in the community has increased during the pandemic.

One study suggests that slower emergency service response times and an increased reluctance among bystanders to perform CPR contributed to reduced survival rates after cardiac arrest.

The authors of the current study list several factors relating to the healthcare system that may have contributed to the surge in cardiac deaths, including:

Increased stress levels among patients in the midst of the crisis may also have played an important role, they write.

The authors conclude:

As COVID-19 cases surge in different regions of the U.S., public health officials and policymakers should improve public health messaging to encourage patients with acute conditions to seek medical care and expand healthcare system resources to mitigate the indirect effects of the pandemic.

They note that their study was based on provisional data from the Centers for Disease Control and Prevention (CDC), which may have been incomplete due to reporting delays.

In addition, some deaths may have been misclassified as cardiovascular deaths when COVID-19 was the actual underlying cause. To support this statement, the authors cite research suggesting that some patients with COVID-19 develop cardiac complications.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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First wave of COVID-19 linked to spike in cardiovascular deaths - Medical News Today

NEW YORK, Nov. 18, 2020 /PRNewswire/ --Elevation Oncology, a clinical-stage biopharmaceutical company focused on the development of precision medicines for patients with genomically defined cancers, announced today a Series B financing of $65 million led by new investors, venBio Partners and Cormorant Asset Management, and the promotion of Shawn M. Leland, PharmD, RPh, the Company's founder, to Chief Executive Officer. Additional participants in the financing include Boxer Capital of Tavistock Group, Janus Henderson, Samsara Biocapital, and Vivo Capital, as well as all of Elevation Oncology's existing investors:Aisling Capital, Vertex Ventures HC, Qiming Venture Partners USA, Driehaus Capital Management, and BVF Partners.

Andrew Phillips, PhD from Cormorant Asset Management, and Richard Gaster, MD, PhD from venBio Partners, will join the Elevation Oncology Board of Directors in conjunction with the new financing.

"We welcome Andy and Rich to our Board of Directors and are encouraged by the support of a highly sophisticated investor group committed to helping us continue to pursue our mission," said Dr. Leland. "At the core of Elevation Oncology is the belief that patients deserve the right clinical team and the right genomic tests to match the right therapeutics to the unique genomic profile of each tumor. We look forward to continuing to work closely with our Board and Scientific Advisors to innovate and accelerate the development of precision oncology therapeutics to realize this vision."

Dr. Lelandfounded Elevation Oncology in July 2019, is a member of its Board of Directors, and previously served as the Company's Chief Business Officer. He has over a decade of experience in medical affairs and business development for the pharmaceutical/biotech industry, with a focus on building collaborations to realize the full potential of targeted and personalized therapeutics. He has been involved in global transactions totaling more than $450 million in upfront payments and milestone payments at Eli Lilly, ARIAD Pharmaceuticals, Argos Therapeutics and Verastem Oncology. Steve Elms, Managing Partner of Aisling Capital, who was serving as Interim CEO of Elevation Oncology, will remain Chair of the Company's Board of Directors.

"Shawn has been instrumental in the founding and success of Elevation Oncology to date," said Mr. Elms. "On behalf of the entire Board of Directors, I express our great confidence in the future of Elevation Oncology under Shawn's leadership. The proceeds raised with the Series B positions the Company well to deliver on our mission of developing precision therapeutics for patients with genomically defined cancers."

Elevation Oncology's lead development program, the Phase 2 CRESTONE study, is evaluating the HER3 monoclonal antibody seribantumab for the treatment of patients with tumors harboring an NRG1 gene fusion. The Company is actively evaluating opportunities for pipeline expansion, prioritizing targeted therapy approaches in tumor types defined by genomic driver alterations.

"The progress that Elevation Oncology has made in the short time since its founding to establish a strong scientific rationale and an accelerated development path for seribantumab in patients with tumors harboring an NRG1 gene fusion is quite impressive," said Dr. Gaster, Partner at venBio. "We see the progress to date as indicative of Elevation Oncology's long-term potential. I look forward to serving on Elevation's Board of Directors as the Company continues to advance its mission to match unique genomic test results with a purpose-built precision medicine approach to enable an individualized treatment plan for each patient."

"Elevation Oncology's commitment to innovation across the drug development lifecycle has drawn a distinguished group of collaborators who are able to broadly conduct genomic testing across the US, rapidly open up clinical trial sites, and ensure exemplary execution of the CRESTONE study," said Dr. Phillips, Managing Director at Cormorant. "I am very pleased to be joining the Company's Board of Directors to support the continued and expanded application of these efforts towards the efficient acquisition, development, and approval of new therapeutics for patients with genomically defined cancers."

Proceeds from the Series B financing will be used to fund the completion of enrollment in the CRESTONE study and other corporate development activities.

About Elevation OncologyElevation Oncology is founded on the belief that every patient with cancer deserves to know what is driving the growth of their disease and have access to therapeutics that can stop it. We make genomic tests actionable by selectively developing drugs to inhibit the specific alterations that have been identified as drivers of disease. Together with our peers we work towards a future in which each unique test result can be matched with a purpose-built precision medicine to enable an individualized treatment plan for each patient. Our lead candidate, seribantumab, inhibits tumor growth driven by NRG1 fusions and is currently being clinically tested in the Phase 2 CRESTONE study for patients with tumors of any origin that have an NRG1 fusion. Details on CRESTONE are available at http://www.NRG1fusion.com. For more information visit http://www.ElevationOncology.com.

About Seribantumab and NRG1 Gene FusionsSeribantumab is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3). HER3 is traditionally activated through binding of its primary ligand, neuregulin-1 (NRG1). The NRG1 gene fusion is a rare genomic alteration that combines NRG1 with another partner protein to create chimeric NRG1 "fusion proteins". The NRG1 fusion protein is often also able to activate the HER3 pathway, leading to unregulated cell growth and proliferation. Importantly, NRG1 gene fusions are mutually exclusive with other known driver mutations and are considered a unique oncogenic driver event essential for tumor cell survival.

NRG1 fusions have been identified in a variety of solid tumors, including lung, pancreatic, gallbladder, breast, ovarian, colorectal, neuroendocrine, and sarcomas. In preclinical experiments, seribantumab prevents the activation of HER3 signaling in cells that harbor an NRG1 gene fusion. In addition to extensive nonclinical characterization and testing, seribantumab has been administered to 847 patients across 12 Phase 1 and 2 studies, both as a monotherapy and in combination with various anticancer therapies. Seribantumab is currently being clinically tested in the Phase 2 CRESTONE study for patients with solid tumors of any origin that have an NRG1 fusion.

About the CRESTONE StudyClinical Study of Response to Seribantumab in Tumors with Neuregulin-1 (NRG1) Fusions. CRESTONE is a Phase 2 tumor-agnostic "basket trial" of seribantumab in patients with any solid tumor that harbor an NRG1 fusion. The primary objective of the study is to describe the anti-tumor activity and safety of seribantumab specifically in patients with an NRG1 gene fusion. CRESTONE offers a clinical trial opportunity for patients with advanced solid tumors who have not responded or are no longer responding to treatment. Patients are encouraged to talk to their doctor about genomic testing of their tumor. CRESTONE is open and enrolling today in the US. For more information visit http://www.NRG1fusion.com.

Media ContactsElevation OncologyName: David Rosen, Argot PartnersPhone: +1 (716) 371-1125Email: [emailprotected]

SOURCE Elevation Oncology

elevationoncology.com

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Elevation Oncology Announces $65M Series B Financing and Promotion of Founder Shawn M. Leland to Chief Executive Officer - PRNewswire

Helixmith said Thursday the first enrolled patient has received its new gene therapy, Engensis (VM202), in phase 3-2 study of diabetic peripheral neuropathy (DPN).

The company plans to continue administering the drug to other participants, as it is screening many additional patients at five clinical trial centers. It is conducting DPN phase 3-2 trials, REGAIN-1A, at 15 clinical centers with 152 enrolled patients in the U.S.

Helixmith aims to meet two endpoints in the study.

The trial's primary efficacy endpoint is to compare changes in average daily pain scores between VM202 and placebo. The secondary endpoint is to reduce pain by 50 percent or more.

DPN is one of the most common complications of diabetes as 30 million U.S. adults have the disorder. Around 28.5 percent of diabetic patients develop DPN, and up to half of them may advance to painful DPN (PDPN).

Dr. Miguel Trevino, head of clinical trials at Innovative Research in which the first patient received VM202, noted that the existing treatments for DPN only relieve pain and show various adverse events with limited efficacy, inevitably leaving half of the patients in painful life.

"The delay of this phase 3 study was due to the preparation of clinical operation system and examining numerous items during the patient's screening process," Helixmith CEO Kim Sun-young said. "Our latest study will add considerable knowledge and evidence to support the optimal use of VM202 in patients needing therapeutic options."

The U.S. Food and Drug Administration recognized the scientific and clinical results of VM202 and designated it as RMAT (regenerative medicine advanced therapy) in 2018.

Continued here:
Helixmith injects DPN therapy into 1st patient of P3 study - Korea Biomedical Review

Laith N AL-Eitan,1 Barakat Z Elsaqa,2 Ayah Y Almasri,1 Hatem A Aman,1 Rame H Khasawneh,3 Mansour A Alghamdi4,5

1Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid 22110, Jordan; 2Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan; 3Department of Hematopathology, King Hussein Medical Center (KHMC), Royal Medical Services (RMS), Amman 11118, Jordan; 4Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabi; 5Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia

Correspondence: Laith N AL-EitanDepartment of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, JordanTel +962-2-7201000 ext 23464Email lneitan@just.edu.jo

Background: Cardiovascular disease is one of the most common causes of morbidity and mortality worldwide. Several cardiovascular diseases require therapy with warfarin, an anticoagulant with large interindividual variability resulting in dosing difficulties. The selected genes and their polymorphisms have been implicated in several Genome-Wide Association Study (GWAS) to be associated with cardiovascular disease.Objective: The goal of this study is to discover if there are any associations between rs646776 of PSRC1, rs660240 and rs12740374 of CELSR2, and rs602633 of SORT1 to coronary heart disease (CHD) and warfarin dose variability in patients diagnosed with cardiovascular disease undergoing warfarin therapy.Methods: The study was directed at the Queen Alia Hospital Anticoagulation Clinic in Amman, Jordan. DNA was extracted and genotyped using the Mass ARRAY system, statistical analysis was done using SPSS.Results: The study found several associations between the selected SNPs with warfarin, but none with cardiovascular disease. All 4 studied SNPs were found to be correlated to warfarin sensitivity during the stabilization phase except rs602633 and with warfarin dose variability at the initiation phase. CELSR2 SNPs also showed association with dose variability during the stabilization phase. Also, rs646776 and rs12740374 were linked to warfarin sensitivity over the initiation phase. Only rs602633 was associated with INR treatment outcomes.Conclusion: The findings presented in this study found new pharmacogenomic associations for warfarin, that warrant further research in the field of genotype-guided warfarin dosing.

Keywords: warfarin, SNPs, pharmacogenetics, Jordan

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Influence of PSRC1, CELSR2, and SORT1 Gene Polymorphisms on the Variab | PGPM - Dove Medical Press

WIRED Health:Tech is one of the most prominent annual conferences exploring technological advances in medicine. This year, the main topics included artificial intelligence, remote surgical systems, and the ongoing fight against COVID-19.

This years WIRED Health:Tech conference took place online last month, in an effort to adapt to the challenges posed by the current pandemic.

A range of specialists held presentations about the latest advances in medical technology, including remote surgical systems, e-health, CRISPR technology, and the issue on everyones mind this year: how research can combat the COVID-19 pandemic.

In this Special Feature, we offer an overview of the panels and main takeaways from the presentations.

Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.

Throughout many of the WIRED Health:Tech presentations, the recurring theme was how technology is helping or hindering the fight against SARS-CoV-2, the coronavirus that has given rise to the current pandemic.

Prof. Heidi Larson from the London School of Hygiene & Tropical Medicine in the United Kingdom spoke of the global response to vaccines, an issue of paramount importance in the context of the pandemic.

Prof. Larson noted that according to her and her colleagues research which appears in The Lancet peoples feelings about vaccines have become far more volatile.

Its a lot more like political opinion polling. They used to be much more stable 1020 years ago. You knew who agreed and who was less confident around vaccines, but thats changing very frequently, she observed.

However, she did offer some positive news:

The overall picture is that [] there is a general trend where people are becoming a little more confident [about vaccines] than they were 5 years ago.

According to Prof. Larson, this may be because public health specialists and communicators are more proactive in dismantling pervasive myths about vaccination over the past few years.

Nevertheless, she cautioned, we do see that Europe remains the lowest in confidence, the most skeptical, with countries like Lithuania [where] only 19% strongly believe that vaccines are safe. The highest [rate] is [in] Finland, at 66% and thats just strongly believe.'

Poland had the most significant drop in confidence in vaccines, she noted.

She also emphasized these fluctuations in confidence in vaccines across the globe occurred before the pandemic. In the current situation, Prof. Larson said, sentiments surrounding vaccinations have become even more volatile.

Because of the hyper-uncertainty and the whole environment of trust and distrust around the COVID vaccine, there are groups that have gotten together to resist even the COVID vaccine, she warned.

The danger of anti-vaccination mentalities can only be mitigated by giving science more of a human face, Prof Larson argued:

We need to bring together the scientific, technological advances that are so valuable, and not lose the human face, but bring that back together [with the scientific perspective]. This isnt just a misinformation problem. This is a relationship problem. This is a cultural revolution, saying we need to change, we need to get back to a more human face in the scientific and medical field.'

Prof. Devi Sridhar a public health advisor and the chair of the Global Public Health department at the University of Edinburgh in the U.K. spoke of the next steps in the fight against the pandemic.

Speaking of the U.K. situation, Prof. Sridhar said that there are certain key actions that the country needs to take to put a stop to the spread of the virus more efficiently:

I think the crucial thing is getting the testing sorted. You need to have a test turnaround time [of] less than 24 hours and have testing widely available. And also [] a strategy: What is the point of a lockdown, what [is] the point of the restrictions?

Other countries have used the lockdown Im thinking of New Zealand, Taiwan, Vietnam, Thailand, Australia [] but theyre using the lockdown to try and eliminate the virus, to get rid of it, and then put in place checks for reimportation, she added.

Prof. Agnes Binagwaho vice chancellor at the University of Global Health Equity in Rwanda went on to speak of the innovations that Rwandan authorities implemented to curb the spread of the new coronavirus in the country.

Prof. Binagwaho said that the first step was to identify both the obstacles and facilitators when it came to stopping the spread of SARS-CoV-2.

According to the expert, having a clear idea of these factors allowed the authorities to establish the best strategy for containing the spread of the virus.

Most importantly, however, according to Prof. Binagwaho, Rwandan authorities made sure to keep its citizens up-to-date with all the daily news regarding the local spread of the virus both good and bad.

[W]hen you need the population to do something to protect itself [] that is not usual, trust counts more than money, she commented.

Some of the technological innovations that the country implemented during the pandemic were robots that take peoples temperatures in airports and hospitals, to limit human contact, and drones that carry supplies to areas that lack appropriate resources.

Prof. Christofer Toumazou from Imperial College London in the U.K. spoke of how technological advances could help during the current pandemic.

Prof. Toumazou, an electronic engineer, created DnaNudge, a fast and accessible DNA testing technology. Its original purpose was helping people understand what health conditions their genetic makeup might predispose them to, so they could make healthier choices.

At WIRED, the researcher and his colleagues said that they adapted this technology to detect COVID-19, creating tests with a turnaround time of only 90 minutes.

In the U.K., the government ordered 5.8 million such tests for state hospitals.

Effectively, it took a pandemic for us to get a technology thats [] prepared for personalized medicine into the hospital system. So the only way that we could bulldoze this was through COVID, Prof. Toumazou noted.

The researcher emphasized just how important this step may be for health, particularly for people with mental health conditions, who would not have to anxiously wait for 48 hours in isolation for their test results.

In a panel discussion, Dr. Indra Joshi director of Artificial Intelligence at NHSx, the U.K. governmental unit responsible for developing national health policies also went on to stress that advanced technology may help not just to better understand the pathology of COVID-19, but also to identify the people who are most at risk.

This, she added, could allow healthcare professionals to provide help faster to those who are likely to be the most affected by infection with the new coronavirus.

In Dr. Joshis view, advances in technology could therefore offer a holistic view of a persons health status and risks, beyond diagnosing COVID-19.

Another panel discussion focused on recent developments in finding a vaccine against the new coronavirus.

The two participants were Tal Zaks, Chief Medical Officer of Moderna Therapeutics, and Prof. Uur ahin, co-founder and CEO of BioNTech.

Both Moderna and BioNTech are testing mRNA candidate vaccines, which use genetic information rather than a viral base to train the immune system against the new coronavirus.

Speaking of the advantages of an mRNA vaccine versus other forms of vaccines, Zaks said that it is better in a number of fundamental ways.

The first is that because we start with genetic information, there is a component of speed that allows you to get into the clinic and then, once youre in the clinic, scale-up manufacturing. Its not by chance that the two leading efforts both leverage mRNA technologies, he pointed out.

I think the second one [] is the biological preciseness so, when you make a recombinant protein, or you otherwise characterize a biologic, the process makes a lot of difference and a lot of things can go wrong. When youre transmitting the [genetic] information, theres no way for the cell to make the wrong bit. So the biological fidelity, if you will, has a higher likelihood to then translate into the kind of immune response you want.

Tal Zaks

I think the last element here is its a very flexible platform, and this takes us a little bit beyond COVID, but the infrastructure required is relatively small and quick, which means, in the manufacturing space, you have tremendous agility that usual technologies dont, Zaks added.

At the time of the WIRED conference, clinical trials for the Moderna and BioNTech candidate vaccines were at similar stages. Since the two approaches have similar premises, the question arises: does this create a sense of competition between the two companies?

According to Zaks, in the context of a pandemic, this is not a valid question. I only have two competitors here: the virus and the clock, he asserted.

He added that should both the Moderna and the BioNTech candidate vaccines demonstrate safety and efficacy, this would be an ideal situation.

The world needs more than one company to succeed here, he said, noting that, if the virus is truly here to stay, as previous research suggests, more than one vaccine may become necessary in the long run.

Prof. ahin agreed:

The way [in which] the whole industry developed vaccines against COVID-19 [] is the best performance of collaboration. Its important to see how people team up for collaboration. Moderna teamed up with the NIH [the National Institutes of Health], we teamed up with Pfizer, AstraZeneca teamed up with Oxford University. So there are several models of collaboration, and we have the strongest transparency in the development of a vaccine.

People see the data almost in real-time coming in, and people understand how [a] phase 1 trial works, how a phase 3 trial works, and Moderna and we even shared our phase 3 protocols so that everyone can see in a transparent fashion how the studies perform and how they are evaluated, Prof. ahin added.

The two researchers also emphasized that this sense of transparency regarding the development of new pharmaceutical products is essential in the long run. They also expressed hope that it may persist after the pandemic subsides.

When asked whether the candidate vaccine development was rushed, so that pharmaceuticals can distribute them sooner rather than later, Prof. ahin explained that the pandemic has caused researchers to find a better, more efficient method of proceeding with clinical trials not a less reliable one.

One important aspect is that instead of skipping [steps] or cutting corners, we decided to do things in parallel. Usually, [in] vaccine development [] you do a phase 1 study, and maybe 6 or 12 months later a phase 2 study, and then decide whether you would do a phase 3 study, he explained.

This is based on minimizing the cost risk, but also based on the traditional way [in which a vaccine] is developed. It is not the best way it is just the traditional way, he also emphasized.

While many of the talks at WIRED Health:Tech revolved around the fight against COVID-19, some also focused on other technological advances in improving patient care.

Dr. Eric Topol founder and director of the Scripps Research TranslationalInstitute talked about using technology to make medicine more humanistic.

The main objective of AI for healthcare and medicine has been to improve accuracy, so that doctors can improve how they diagnose disease and care for their patients, he observed.

This is what is known as precision medicine. But Dr. Topol believes that using AI in medical practice could bring about more far-reaching benefits.

This could include freeing healthcare practitioners from tasks, such as filing information about their patients into digital systems, so that they can pay more attention to their patients.

Medicine has eroded terribly its a rushed job, Dr. Topol asserted in his talk. We see patients in a single-digit number of minutes, and thats not enough.

You need the gift of time, which AI can give back so that people dont feel so rushed and doctors and nurses and clinicians dont feel so rushed either. [] We want to have clinicians and doctors spending more time with patients and less time [at the computer] keyboard.

Dr. Pearse Keane a National Institute for Health Research clinician-scientist at the Institute of Ophthalmology at University College London spoke of how doctors could soon use AI algorithms to diagnose and treat early-stage retinal diseases a set of eye problems that can lead to vision loss.

Dr. Keane made a similar point to Dr. Topols argument, stressing that so many people are affected by eye diseases in the U.K. that specialists are often overwhelmed by the sheer amount of patients waiting for diagnosis and treatment.

Some people are essentially going blind because they cannot be seen and treated early enough, Dr. Keane said. But new technologies and in particular, AI, have at least some role in addressing this problem, he added.

Dr. Keane and colleagues from Moorfields Eye Hospital collaborated with scientists specializing in using the AI technology DeepMind, in demonstrating how to train the system to diagnose retinal diseases correctly and fast-track referrals for specialist treatment.

The researchers published the results of their study in Nature Medicine in 2018. Now, Moorfields Eye Hospital are building a new care and research center, with plans to integrate more advanced technology into this setting.

But Dr. Keane argues that clinical AI help by linking various health data, therefore offering a bigger picture of a persons overall health status and health risks.

Dr. Mark Slack chief medical officer and co-founder of CMR Surgical spoke of the potential of Versius, a surgical robotic system that can help specialists carry out minimally invasive keyhole surgery.

Is keyhole surgery better than open surgery? There are huge advantages for keyhole surgery, Dr. Slack asserted in his presentation.

If you have a large wound [following open surgery], about 50% of those patients will go back to the hospital. If you have a small, minimal-access wound, almost none will go back. If you have a large wound, about a fifth of patients will be required to go back into [the operating] theater if they get a wound infection [] [but] roughly 50% of complications are reduced by having keyhole surgery rather than open [surgery].

Dr. Mark Slack

Finally, Prof. Jennifer Doudna a biochemist at UC Berkeley and founder of the Innovative Genomics Institute, who co-invented CRISPR technology spoke of the revolutionary potential of gene editing. This new technology has taken the medical research world by storm.

Prof. Doudna described gene-editing technology as molecular surgery its a way to alter the DNA in cells and organisms in ways that allow precise correction of disease-causing [genetic] mutations and also allow scientists to do all sorts of other kinds of manipulations of genetic material on living cells and organisms, she explained.

One way in which gene-editing tools might be helpful, she said, might be by helping treat severe blood disorders such as sickle cell disease. Other applications might be in the treatment of eye diseases or even muscular dystrophy.

The scientist explained that, besides CRISPR technologys potential in treating disease, it could also come in handy when detecting viruses, including the new coronavirus.

She even suggested that in the coming months, there may be a CRISPR-based point-of-care diagnostic tool that could help doctors identify infections much faster.

She concluded her talk by noting that:

The potential of this technology continues to advance. I think the keys will be delivery and control of the editing and, of course, ensuring safety, effectiveness, and access. The possibilities are extraordinary its really an exciting time to be working in this field.

For live updates on the latest developments regarding the novel coronavirus and COVID-19, click here.

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WIRED Health:Tech 2020: Latest advances and the fight against COVID-19 - Medical News Today

Chongtao Du,1,* Yuyang Feng,1,* Guizhen Wang,2 Zhiyuan Zhang,1 Huimin Hu,1 Yu Yu,1 Jiayang Liu,1 Lihao Qiu,1 Hongtao Liu,1 Zhimin Guo,3 Jing Huang,3 Jiazhang Qiu1

1Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun 130062, Peoples Republic of China; 2College of Food Engineering, Jilin Engineering Normal University, Changchun 130052, Peoples Republic of China; 3Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: Jiazhang QiuCollege of Veterinary Medicine, Jilin University, No. 5333 Xian Road, Changchun 130062, Peoples Republic of ChinaEmail qiujz@jlu.edu.cnJing HuangDepartment of Clinical Laboratory, The First Hospital of Jilin University, Changchun 130021, Peoples Republic of ChinaEmail huangj@jlu.edu.cn

Objective: A colistin-resistant Escherichia coli strain isolated from dog feces was characterized in this study.Methods and Results: A multiplex PCR assay was used to detect the presence of colistin-resistant mcr genes; it was found that E. coli QDFD216 co-harbored the mcr-1 and mcr-3 genes. Whole-genome sequencing and further bioinformatics analysis revealed that E. coli QDFD216 belonged to serotype O176:H11, fimH1311 type and ST132. The resistance genes blaCTX-M-14, mdfA, dfrA3, acrA, acrB, tolc, and sul3 were present in the chromosome. The mcr-1.1 and mcr-3.7 genes were located in two plasmids of different incompatibility groups. mcr-1.1 was carried by a IncX4-type plasmid within an typical IS 26-parA-mcr-1.1-pap2 cassette, while mcr-3.7 was encoded by an IncP1-type plasmid with a genetic structure of TnAs2-mcr-3.7-dgkA-IS 26. No additional antibiotic resistance genes were carried by either plasmid.Conclusion: This is the first report of an E. coli isolate co-harboring a mcr-1.1-carrying IncX4 plasmid and a mcr-3.7-carrying IncP1 plasmid. The evolution and mechanism of mcr gene co-existence need further study to assess its impact on public health.

Keywords: colistin resistance, whole-genome sequencing, mcr genes, mcr-1, mcr-3

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Co-Occurrence of the mcr-1.1 and mcr-3.7 Genes in a Multidrug-Resistan | IDR - Dove Medical Press