Researchers Discover Molecular Switch That Repairs Neurological Damage - Interesting Engineering

Curing disorders such as multiple sclerosis could one day be as simple as turning on a molecular switch thanks to new research by Isobel Scarisbrick, Ph.D., published in the Journal of Neuroscience. Her work finds that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin.

RELATED: NEW MOLECULE LINKED TO STOPPING AND REVERSING NEURO DAMAGE DONE BY PARKINSON’S DISEASE

Improving function

"Myelin regeneration holds tremendous potential to improve function. We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system does have a good capacity for innate repair," said Dr. Scarisbrick, principal investigator, and senior author. "This sets the stage for development of new clinically relevant myelin regeneration strategies."

Myelin is an insulating layer, made up of protein and fatty substances, that forms around nerves, including those in the brain and spinal cord. It protects electrical signals sent through the nervous system. 

Once myelin is injured, electrical signals between brain cells are slowed down. This results in the loss of sensory and motor function you so often see in disorders such as Multiple Sclerosis.

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Robotic exoskeleton helps woman with multiple sclerosis walk - WJXT News4JAX

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Despite having Multiple Sclerosis, Kathy Miska can walk with the assistance of a robotic exoskeleton that is programmed to meet her needs. (Cleveland Clinic News Service)

Kathy Miska, 56, of Strongsville, Ohio is fighting Multiple Sclerosis one step at a time.

Multiple Sclerosis, or MS, disrupts signals from the brain and often robs people of their mobility.

Miska is one of five MS patients at Cleveland Clinic taking part in a research study to see if a special robotic brace, or exoskeleton, will benefit her mobility.

“By doing what we would call a ‘forced use,’ the hope is that you’ll reprogram the brain so that it actually can work better and create better walking,” said Francois Bethoux, M.D., Chair of Cleveland Clinic’s Department of Physical Medicine and Rehabilitation and principal investigator of the study.

The device is programmed to each person who uses it. Braces support the lower body and carry the user. Motors are triggered by sensors to lift the legs, assisting the patient to walk.

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Principia Biopharma - The Future Worsens - Seeking Alpha

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GW Pharmaceuticals’ Cannabis-Based Epilepsy Drug Sales Grow - Barron's

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An employee holds a crate of bottles Epidiolex, a cannabinoid-based medicine, at the GW Pharmaceuticals facility in Sittingbourne, U.K. Photograph by Jason Alden/Bloomberg

Ahead of its appearance at this week’s J.P. Morgan Healthcare Conference, GW Pharmaceuticals, the only company with an approved drug derived from cannabis, says that 2019 sales came in better than expected.

The British drug company said on Sunday that its seizure treatment Epidiolex achieved sales of $104 million in the December quarter and $296 million in 2019—its first year of sales.

Its stock (ticker: GWPH) rose 5% on the news, to $113.31. Its preannounced sales for the fourth quarter were somewhat better than predicted by admirers like Guggenheim’s Yatin Suneja, and the analyst wrote on Monday that he came away reassured about his Buy rating after talking to GW’s management.

A rush of Buy recommendations followed the launch of Epidiolex after the U.S. Food and Drug Administration approved it as a treatment for difficult forms of epilepsy. The drug started strong, and GW stock soared to $196 a share, before sinking amid the cannabis sector selloff in last year’s second half.

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Concerto HealthAI Establishes Real-World Data and AI Collaboration with Janssen - P&T Community

BOSTON, Jan. 13, 2020 /PRNewswire/ -- Concerto HealthAI, a market leader for Real-World Data (RWD) and enterprise AI technology solutions for Precision Oncology, announced today that it has entered into a multi-disease collaboration with Janssen Research & Development, LLC (Janssen). The collaboration will allow Janssen to access Concerto HealthAI's use-case engineered RWD, enterprise AI solutions, and scientific services. Concerto HealthAI has the most comprehensive, representative, and independently sourced RWD in the industry as part of an exclusive licensing agreement with the American Society of Clinical Oncology's CancerLinQ® program, and partnerships with clinically integrated community oncology networks, and other partners.

Janssen gains access to Concerto HealthAI's powerful suite of use-case engineered RWD products in the new eurekaHealth 3.0 enterprise AI solution. eurekaHealth integrates and enriches multiple sources to provide a holistic view of the patient journey with greater clinical depth to support translational sciences, clinical study design, and RWD applications for regulatory submissions. eurekaHealth 3.0 is the only enterprise-grade solution to exceed 21CFRPart11 compliance requirements and serve as an intelligence layer, integrating into research and clinical development workflows across the enterprise. Janssen will be the first to use Concerto HealthAI's Genome360™, a translational-grade, first-in-class, real-world solution in development that integrates in-depth clinical and next-generation sequencing characterization of a patient's cancer.

"We believe our mission and responsibility as a leader in Precision Oncology aligns well with Janssen's innovation focus in data science," said Jeff Elton, PhD, CEO of Concerto HealthAI. "We are excited to bring our unique integration of RWD, technology applications, and data science expertise to collaborate with Janssen's researchers and data scientists to optimize drug development for patients."

About Concerto HealthAI
Concerto HealthAI, a SymphonyAI Group portfolio company, is a technology leader in definitive Real-World Data (RWD) and AI solutions for Precision Oncology. Our mission is to bring together unique data assets, leading AI-based technologies, and the world's top outcomes research and data science talent. Our focus is on revolutionizing clinical and outcomes research to accelerate the insights benefitting patient treatment. For more information, visit us at http://www.concertohealthai.com.

View original content:http://www.prnewswire.com/news-releases/concerto-healthai-establishes-real-world-data-and-ai-collaboration-with-janssen-300985616.html

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Cortica Announces Leadership Appointments And Strategic Investment By Ajax Health And Questa Capital - P&T Community

SAN DIEGO, Jan. 13, 2020 /PRNewswire/ -- Cortica Inc. ("Cortica"), a leading provider of advanced neurological therapies for children with autism and other neurodevelopmental conditions, announced today leadership appointments to further its mission to design and deliver life-changing care – one child, one family, one community at a time.

"We are thrilled to have attracted a team of leaders and investor partners with a proven record of success and an unwavering commitment to helping children with neurodevelopmental differences and their families," said Neil Hattangadi, MD, Co-Founder and Chief Executive Officer at Cortica. "These leaders will help us accelerate the rollout of our comprehensive care model for autism nationally and support ongoing technological innovation for clinical care delivery and the patient experience."

The following operational leadership team will help position Cortica for its next phase of growth.

Daniel Virnich, MD, MBA, Chief Operating Officer: Dr. Virnich brings over 15 years of healthcare leadership experience to Cortica. He was previously President, Florida Market, for DaVita, Inc./Healthcare Partners. In this role he was responsible for growth, operations, and clinical quality of a $1 billion delegated medical group, serving approximately 100,000 Medicare Advantage patients. He previously served as Senior Vice President, California Market, for DaVita and National Chief Medical Officer, Acute Care Services, for Team Health Inc. Dr. Virnich earned his MD from the University of Chicago and his MBA from the Kellogg School of Management at Northwestern; he completed his clinical training at UCLA Medical Center and is board-certified in Internal Medicine.

"Cortica has developed an innovative, neuroscience-based care model to treat a very important and underserved population," said Dr. Virnich. "As COO, I am committed to operational excellence that enables strong clinical outcomes, a great experience for families and the well-being of Cortica's team members."

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The $432B Medical Devices Market: Worldwide Trends, Forecasts and Competitive Analyses (2014-2025) - P&T Community

DUBLIN, Jan. 13, 2020 /PRNewswire/ -- The "Medical Device Market Report: Trends, Forecast and Competitive Analysis" report has been added to ResearchAndMarkets.com's offering.

The medical device market is expected to reach an estimated $432.6 billion by 2025, and it is forecast to grow at a CAGR of 4.1% from 2020 to 2025.

Some features of this report include:

Market size estimates: Medical device market size estimation in terms of value ($B) shipment. Trend and forecast analysis: Market trend (2014-2019) and forecast (2020-2025) by region, application and end-user industry Segmentation analysis: Medical device market size by application, function, and end-use in terms of value and volume shipment. Regional analysis: Medical device market breakdown by key regions such as North America, Europe, and Asia & Rest of World. Growth opportunities: Analysis on growth opportunities in different applications and regions of a medical device in the medical device market. Strategic analysis: This includes M&A, new product development, and competitive landscape of medical device in the medical device market. Analysis of the competitive intensity of the industry based on Porter's Five Forces model.

The future of the medical device market looks good with opportunities in the hospital and homecare sectors. The major drivers for market growth are increasing healthcare expenditure, technological development, growing aging population, and chronic diseases.

Emerging trends, which have a direct impact on the dynamics of the medical device industry, include increasing use of AI-Optimized medical device, increasing acceptance of wearable medical devices, growing use of miniaturized medical devices, and growing adoption 3D-Printing in medical devices.

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Novartis, Merck and Allergan join those raising U.S. drug prices for 2020 - Reuters

NEW YORK (Reuters) - Novartis AG, Merck & Co Inc and Allergan Plc were among companies that raised U.S. prices on more than 100 prescription medicines on Friday, bringing the tally to 445 drugs that will cost more in 2020, according to data analyzed by healthcare research firm 3 Axis Advisors.

FILE PHOTO: Pharmaceutical tablets and capsules are arranged in the shape of a U.S. dollar sign on a table in this picture illustration taken in Ljubljana August 20, 2014. REUTERS/Srdjan Zivulovic

That is above the average of 404 drug price increases in the first three days of January over the past five years. Nearly all of the price increases are below 10%, with the median price increase around 5%, according to 3 Axis.

Swiss drugmaker Novartis raised prices on nearly 30 drugs including psoriasis treatment Cosentyx and Multiple Sclerosis medicine Gilenya, 3 Axis said. Most of those increases were in the range of 5.5% to 7%.

Novartis said that while it is raising the list prices of about 7 percent of its U.S. medicines, after discounts and rebates to commercial and government payers it expects a net price decrease of 2.5% in 2020.

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Research Explores Cannabis as Treatment for MS, Alzheimer’s and Huntington’s Disease - Pain News Network

By Pat Anson, PNN Editor

The University of Alberta is partnering with a Canadian cannabis company in three research projects exploring the use of medical cannabis for the treatment of Multiple Sclerosis, Alzheimer’s and Huntington’s diseases. 

Atlas Biotechnologies is investing nearly $300,000 over the next two years to fund the studies. Atlas operates a 38,000 square foot cannabis production facility near Edmonton and will supply customized blends of cannabis products to U of A researchers.

“People are touting (cannabis) for all kinds of things, but without solid scientific evidence,” said Ross Tsuyuki, PharmD, chair of the Department of Pharmacology at U of A. “But there likely are benefits for some conditions.”

The most well-known chemical compounds in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD), but the plant has hundreds of other active biological chemicals, each with the potential of having therapeutic benefits. The goal of the research is to identify what specific compounds or combinations of compounds are effective.

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Smoking may increase risk of stroke - Taipei Times

A doctor warned that smokers could increase their risk of having a stroke by 12 percent and they run a 1.81 times greater risk of developing Multiple Sclerosis.

Health Promotion Administration (HPA) data show that as many as 35.6 percent of recovering male heart attack patients and 20 to 30 percent of males recovering from a stroke do not quit smoking, Mackay Memorial Hospital deputy superintendent Yeh Hung-yi (葉宏一) said.

The statistics show that public knowledge of the risks to cardiovascular health from smoking remains inadequate, he said.

Conversely, 77.8 percent of people with lung cancer are males and only 7.7 percent of them continue to smoke after they recover from lung cancer, Yeh said.

Heart disease, cerebrovascular disease and conditions related to high blood pressure have all been among the top 10 causes of death in Taiwan since the government began keeping statistics, he said, adding that the three causes combined accounted for nearly 40,000 deaths in the nation last year.

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Friday, January 3, 2020 - California Healthline

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Despite Intense Public, Congressional Scrutiny, Pharma Still Hikes Prices For Hundreds Of Drugs In 2020 - Kaiser Health News

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ThermoGenesis Holdings Announces That ImmuneCyte Joint Venture Receives $3.0 Million Equity Investment - P&T Community

RANCHO CORDOVA, Calif., Jan. 3, 2020 /PRNewswire/ -- ThermoGenesis Holdings, Inc. (Nasdaq: THMO), a market leader in automated cell processing tools and services in the cell and gene therapy field, today announced that ImmuneCyte Life Sciences, Inc. ("ImmuneCyte"), an 80/20 joint venture between HealthBanks Biotech (USA) and ThermoGenesis, has closed a $3.0 million equity investment with a private institution. The investor received 600,000 shares of Class A common stock at $5.00 per share, representing a 5.66% ownership in the joint venture. As a result of this equity investment in ImmuneCyte, ThermoGenesis' equity in the joint venture is no longer subject to the anti-dilution provision. After this investment, ImmuneCyte is owned 75.47% by HealthBanks Biotech (USA), 18.87% by ThermoGenesis Holdings and 5.66% by the private institution.

ImmuneCyte is a joint venture which was created in order to provide immune cell banking services to healthy customers, enabling them to store their healthy immune cells for potential future use in immunotherapies, leveraging ThermoGenesis' proprietary CAR-TXpress™ platform and HealthBanks' global, stem cell banking network. ImmuneCyte isolates healthy immune cells from 150-200ml of peripheral blood with a proprietary, automated cell processing platform developed by ThermoGenesis, which makes ImmuneCyte the first cell bank capable of processing immune cells under a functionally-closed and fully cGMP compliant environment, a quality control element which is essential for cell and gene therapies.  

"The rapid closing of this equity investment in ImmuneCyte, only shortly after the establishment of the joint venture, reflects a significant interest in ThermoGenesis' proprietary technology and the growth potential of ImmuneCyte's business model," said Chris Xu, PhD, Chief Executive Officer of ThermoGenesis. "We are excited by this latest investment, which will allow the joint venture to further accelerate its growth, while serving to increase the value of ThermoGenesis' equity stake in the joint venture, long-term."

About ImmuneCyte Life Sciences, Inc.
ImmuneCyte will provide clients with the opportunity to bank their own immune cells when the cells are "healthy and unaffected," as a future resource for cellular immunotherapies, such as CAR-T. ImmuneCyte utilizes ThermoGenesis' proprietary CAR-TXpress™ platform, a GMP compliant closed-system capable of automated separation and cryopreservation of different components from blood. For more information about ImmuneCyte Life Sciences Inc., please visit: www.immunecyte.com.  

About ThermoGenesis Holdings, Inc.
ThermoGenesis Holdings, Inc., formerly known as Cesca Therapeutics Inc., develops, commercializes and markets a range of automated technologies for CAR-T and other cell-based therapies. The Company currently markets a full suite of solutions for automated clinical biobanking, point-of-care applications, and automation for immuno-oncology, including its semi-automated, functionally-closed CAR-TXpress™ platform, which streamlines the manufacturing process for the emerging CAR-T immunotherapy market. For more information about ThermoGenesis, please visit: www.ThermoGenesis.com

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10 Worst-Performing Stocks of 2019 - Motley Fool

The stock market continued its bull run this year, with all the major indexes on track to end 2019 with double-digit gains. Stocks are setting new highs despite warnings of a looming recession. The S&P 500 set 19 new all-time highs in 2019, and that's after 18 new highs in 2018. 

Despite the booming market, a lot of underperformers saw their stocks plummet during the year for reasons in and out of their control. We're not talking 8% year-to-date (YTD) declines. These are high-double-digit-percentage sell-offs that companies may never recover from. 

With that in mind, here's a look at 10 of the worst-performing stocks of 2019. 

Image source: Getty Images.

1. Macy's -- down 45.3% YTD

Department store operator Macy's (NYSE:M) has had a tough time of it, even if consumers are opening their wallets this holiday season. 

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Global Wearable Adhesive Market Growth, Trends, and Forecast Report 2019-2024 - ResearchAndMarkets.com - Business Wire

DUBLIN--(BUSINESS WIRE)--The "Wearable Adhesive Market - Growth, Trends, and Forecast (2019 - 2024)" report has been added to ResearchAndMarkets.com's offering.

The wearable adhesive market is expected to register a CAGR of 13.15% during the forecast period 2019 - 2024

With the advent of wireless mobile technology in wearable sensors, healthcare professionals are able to remotely monitor a patient's biometric data, such as blood pressure, heart rate, and blood glucose level.

In recent years, developers of adhesives, trying to attach wearable devices to the skin have faced many types of physical, and design challenges. In order to work properly, these devices have to be properly stuck to the body, necessitating the design and development of new adhesives.Wearable products are used as handheld monitoring tools and have applications in identification and monitoring of diseases. Owing to the growth in chronic diseases, more patients are opting for home healthcare as it is cost-effective and an efficient way of treatment, rather than hospital services, which is expected to drive the wearables demand.However, developing adhesives for wearable applications is not an easy task. Designers can create effective products only by analyzing the skin type and age of the target patient population and by understanding the physical properties of the wearable devices.

Key Market Trends

Sports and Fitness Wearables Demand to Augment the Market Growth

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Endonovo Therapeutics Provides SofPulse® To All NFL Teams [Updated] - GlobeNewswire

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December 23, 2019 09:48 ET|Source:Endonovo Therapeutics, Inc.

Los Angeles, CA, Dec. 23, 2019 (GLOBE NEWSWIRE) -- Endonovo Therapeutics, Inc. (OTCQB: ENDVD) ("Endonovo" or the "Company"), announced today the delivery of SofPulse® evaluation units to all thirty-two National Football League (“NFL”) teams.

Alan Collier, CEO of Endonovo Therapeutics stated, “With injuries affecting the NFL more than any other professional sports league, we are pleased to support the health of NFL players by providing SofPulse® evaluation units to all NFL teams. The SofPulse® device is clinically proven to reduce post-operative pain, swelling and need for opioids. Endonovo is committed to helping NFL players get back on the field faster when recovering from medical procedures caused by injuries. We are currently expanding our sales and marketing efforts to other leagues and all levels, from high school to professional athletes.”

Dr. Nev Zubcevik, Harvard trained Physical Medicine and Rehabilitation specialist with years of experience serving professional athletes, and Chief Medical Officer of Endonovo Therapeutics said, “The microcurrents in SofPulse® reduce swelling and speed up the natural recovery process. The SofPulse® technology treats swelling and reduces inflammation by improving blood flow. We believe that injured NFL players undergoing medical procedures will benefit greatly from the SofPulse® technology.”

About Endonovo Therapeutics

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The 10 Most Interesting People WDET Met In 2019 - WDET

The reporters and producers at 101.9 WDET meet a lot of people in the course of our work. 

Some of them are well-known politicians, artists and other change-makers. Some are Detroiters fighting to make their community better. Others are simply going about their lives. 

Here are the most interesting people we’ve met in 2019, as decided by our audience through our most read and listened to stories, podcast episodes and other interviews. See that list below.

“Everybody started yelling, ‘Grandma Techno! Grandma Techno!’ And then it went viral. I’m known all over the world that way.” - Patricia Lay-Dorsey

Stephen Bondio

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Primary Progressive Multiple Sclerosis Treatment Market Studied by 2019-2027 with Profiling Player - Market Research Sheets

New Statistical Research for Primary Progressive Multiple Sclerosis Treatment market 2019 displays the latest industry insights with future trends and analysis of the products and services, enabling you to deeply penetrate the Primary Progressive Multiple Sclerosis Treatment market with high profitability.

The New “Primary Progressive Multiple Sclerosis Treatment Market 2019: Global Industry Analysis, Share, Growth, Trends and Forecasts to 2019 – 2027” report offers an in-depth Study of all Latest Advancement in the Primary Progressive Multiple Sclerosis Treatment Industry. The Primary Progressive Multiple Sclerosis Treatment report offers the plus points as well as weaknesses of the established market players. It analyses numerous features of the global Primary Progressive Multiple Sclerosis Treatment market such as demand, drivers, challenges, and options. The report appraises the influence of these aspects on each market region during the estimated time. It presents the value chain analysis together with vendor list and highlights the present market situation between consumer and supplier.

Download PDF Brochure @ https://www.worldwidemarketreports.com/sample/272000

Major players operating in the Global Primary Progressive Multiple Sclerosis Treatment market include: F. Hoffmann-La Roche Ltd., Genzyme Corporation, Glialogix, Inc., Kyorin Pharmaceutical Co., Ltd., MedDay SA, Santhera Pharmaceuticals Holding AG, Teva Pharmaceutical Industries Ltd.

The report covers a forecast and an analysis of the Primary Progressive Multiple Sclerosis Treatment market on a global and regional level. The study provides historical data till 2018 along with a forecast from 2019 to 2027 based on revenue (USD Million). The study includes drivers and restraints of the Primary Progressive Multiple Sclerosis Treatment market along with the impact they have on the demand over the forecast period. Additionally, the report includes the study of opportunities available in the Primary Progressive Multiple Sclerosis Treatment market on a global level.

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TG Therapeutics Announces $50.0 Million Registered Direct Public Offering of Common Stock to a Single Institutional Investor - GlobeNewswire

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December 23, 2019 07:30 ET|Source:TG Therapeutics, Inc.

NEW YORK, Dec. 23, 2019 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), today announced it has entered into a definitive agreement to sell approximately 5.4 million shares of registered common stock of the Company at $9.20 per share, to a single, biotechnology-focused, institutional investor as a registered direct public offering. Proceeds from the sale are expected to be approximately $50.0 million. TG Therapeutics intends to use the net proceeds from the offering to fund the ongoing development and commercialization of the Company’s lead assets, ublituximab and umbralisib, as well as for research and development activities of the Company’s pipeline, and for general corporate purposes. The offering is expected to close on or about December 23, 2019, subject to customary closing conditions.

Michael S. Weiss, the Company's Executive Chairman and Chief Executive Officer, commented on the transaction, “We are excited to have completed this unsolicited financing with a premier biotechnology investor and believe it represents a major vote of confidence in our drug candidates and current pivotal programs. Following this financing, we expect to end 2019 with approximately $140 million in cash and cash equivalents, providing us a cash runway well into 2021, and importantly through our upcoming major milestones including the UNITY-NHL MZL NDA submission for umbralisib, as well as the data readouts for both the UNITY-CLL Phase 3 trial and the ULTIMATE I & II Phase 3 trials in Multiple Sclerosis.” 

The shares described above are being offered by TG Therapeutics pursuant to a registration statement previously filed with and subsequently declared effective by the Securities and Exchange Commission (“SEC”). A prospectus supplement relating to the offering has also been filed with the SEC and is available on the SEC’s website at http://www.sec.gov. Copies of the prospectus supplement and the accompanying base prospectus relating to this offering may be obtained at the SEC's website at http://www.sec.gov or by contacting TG Therapeutics, Inc., 2 Gansevoort Street, 9th Floor, New York, NY, Attention: Corporate Secretary, 212-554-4484.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

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Severe type I interferonopathy and unrestrained interferon signaling due to a homozygous germline mutation in STAT2 - Science

Interferon Insight

Uncontrolled type I IFN activity has been linked to several human pathologies, but evidence implicating this cytokine response directly in disease has been limited. Here, Duncan et al. identified a homozygous missense mutation in STAT2 in siblings with severe early-onset autoinflammatory disease and elevated IFN activity. STAT2 is a transcription factor that functions downstream of IFN, and this STAT2R148W variant was associated with elevated responses to IFNα/β and prolonged JAK-STAT signaling. Unlike wild-type STAT2, the STAT2R148W variant could not interact with ubiquitin-specific protease 18, which prevented STAT2-dependent negative regulation of IFNα/β signaling. These findings provide insight into the role of STAT2 in regulating IFNα/β signaling in humans.

Abstract

Excessive type I interferon (IFNα/β) activity is implicated in a spectrum of human disease, yet its direct role remains to be conclusively proven. We investigated two siblings with severe early-onset autoinflammatory disease and an elevated IFN signature. Whole-exome sequencing revealed a shared homozygous missense Arg148Trp variant in STAT2, a transcription factor that functions exclusively downstream of innate IFNs. Cells bearing STAT2R148W in homozygosity (but not heterozygosity) were hypersensitive to IFNα/β, which manifest as prolonged Janus kinase–signal transducers and activators of transcription (STAT) signaling and transcriptional activation. We show that this gain of IFN activity results from the failure of mutant STAT2R148W to interact with ubiquitin-specific protease 18, a key STAT2-dependent negative regulator of IFNα/β signaling. These observations reveal an essential in vivo function of STAT2 in the regulation of human IFNα/β signaling, providing concrete evidence of the serious pathological consequences of unrestrained IFNα/β activity and supporting efforts to target this pathway therapeutically in IFN-associated disease.

INTRODUCTION

Type I interferons (including IFNα/β) are antiviral cytokines with pleiotropic functions in the regulation of cellular proliferation, death, and activation. Reflecting their medical importance, type I IFNs have been shown to be essential to antiviral immunity in humans (1), whereas their potent immunomodulatory effects have been exploited to treat both cancer and Multiple Sclerosis (2, 3).

IFNα/β also demonstrates considerable potential for toxicity, which became apparent in initial studies in rodents (4) and subsequent clinical experience in patients (5, 6). Thus, the production of and response to type I IFNs must be tightly controlled (7). Transcriptional biomarker studies increasingly implicate dysregulated IFNα/β activity in a diverse spectrum of pathologies ranging from autoimmune to neurological, infectious and vascular diseases (811).

The immunopathogenic potential of IFNα/β is exemplified by a group of monogenic inborn errors of immunity termed “type 1 interferonopathies,” wherein enhanced IFNα/β production is hypothesized to be directly causal (12). Neurological disease is typical of these disorders, which manifest as defects of neurodevelopment in association with intracranial calcification and white matter changes on neuroimaging, suggesting that the brain is particularly vulnerable to the effects of excessive type I IFN activity (9). A spectrum of clinical severity is recognized, from prenatal-onset neuroinflammatory disease that mimics in utero viral infection—Aicardi-Goutières syndrome (13)—to a clinically silent elevation of IFN activity (14).

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