Developing new stem cell therapies requires more than a solo biologist having a eureka moment alone in the lab. Real progress relies on collaborations between biologists, engineers and physicians. Thats why The Eli and Edythe Broad Foundation has continued its support of two strategic initiatives: innovation awards bringing together teams of engineers and scientists from USC and Caltech, and clinical research fellowships for physician-scientists.

Engineering new approaches: The Broad Innovation Awards

For the fifth consecutive year, the Broad Innovation Awards are providing critical funding to USC-affiliated faculty members pursuing multi-investigator research collaborations related to stem cells. For the first year, these collaborations are also drawing on the expertise of biomedical engineers from Caltech. Each award provides $200,000 of funding for a one-year project.

Were very excited to be joining our colleagues at USC in pioneering new approaches to advancing stem cell research, said Stephen L. Mayo, chair of the Division of Biology and Biological Engineering at Caltech. Were thankful to The Broad Foundation for supporting cross-town collaborations between scientists with different expertise but common goals.

With support from a Broad Innovation Award, Andy McMahon, the director of the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, is collaborating with Caltech biomedical engineer Long Cai to leverage a new technology for understanding chronic kidney disease. The technology, called seqFISH, provides information about genetic activity taking place in intact tissueenabling the study of the interactions between cells in their native environments.

Dr. Cais seqFISH technology will provide an unprecedented insight into the cellular interplay underlying chronic kidney disease caused by a maladaptive response to acute kidney injury, said McMahon, who is the W.M. Keck Provost and University Professor of Stem Cell Biology and Regenerative Medicine, and Biological Sciences, as well as the chair of the Department of Stem Cell Biology and Regenerative Medicine at USC. We aim to better understand this maladaptive responsewhich is more common in malesin order to find new targets for preventing the progression to chronic kidney disease.

A second Broad Innovation Award brings together USC Stem Cell scientist Rong Lu and Caltech synthetic biologist Michael Elowitz. Their team will study the spatial organization of blood-forming stem and progenitor cells, also called hematopoietic stem and progenitor cells (HSPCs), which reside in the bone marrow. By pinpointing the locations of specific HSPCs, the scientists may find clues to explain why certain HSPCs are so dominantreplenishing the majority of the bodys blood and immune cells after a disruption such as a bone marrow transplantation.

Spatial advantages may be the primary drivers of what we refer to as the clonal dominance of certain HSPCs, said Lu, a Richard N. Merkin Assistant Professor of Stem Cell Biology and Regenerative Medicine, Biomedical Engineering, Medicine, and Gerontology at USC. Understanding the spatial competition between HSPCs could help improve bone marrow transplantation and provide new insights into aging and the development of diseases such as leukemiawhich are associated with clonal dominance.

Elowitz added: Thanks to the Broad Innovation Award and this exciting collaboration with Rong Lu, we will be able to bring a new, synthetic biology approach to record cell histories and read them out in individual cells within their native spatial context, providing new insights into fundamental questions in blood stem cell development.

A third Broad Innovation Award brings together three collaborators at USC: Michael Bonaguidi, an assistant professor of stem cell biology and regenerative medicine, biomedical engineering, and gerontology; Robert Chow, a professor of physiology and neuroscience, and biomedical engineering; and Jonathan Russin, an assistant professor of neurological surgery and associate surgical director for the USC Neurorestoration Center. Their project focuses on finding new approaches to treating epilepsy by studying neural cells called astroglia. These cells perform a variety of key functions that support the health of neurons in the brain, and they may also play a role in modulating epileptic seizures.

Although adults dont tend to generate many new brain cells, humans do produce a limited number of new astroglia, said Bonaguidi. We will examine these newborn astroglia at the single-cell level to better understand their role in epileptic patients, and to lay the groundwork for identifying new treatments.

The doctors are in: The Broad Clinical Research Fellowships

The Broad Clinical Research Fellowships are also entering their fifth consecutive year. These fellowships support stem cell research by physician-scientists and residents who intend to practice medicine in California.

These fellowships provide a very special opportunity for our medical residents to engage deeply in laboratory research, as a complement to their extensive training in patient care, said Laura Mosqueda, Dean of the Keck School of Medicine of USC. This valuable research experience gives them a much more complete perspective on how to meet the challenges of finding the best possible treatments for their patients.

A USC resident physician in general surgery, Kemp Anderson will spend his fellowship studying necrotizing enterocolitis, a very serious intestinal infection that affects nearly 10 percent of premature infants. Specifically, he will explore how a molecule involved in cellular communication, called farnesoid X receptor, or FXR, might contribute to this disease.

If FXR plays a role in compromising intestinal barrier function in these premature infants, then altering the activity of FXR could potentially yield treatment modalities for necrotizing enterocolitis, avoiding the morbidity and mortality associated with surgical intervention, said Anderson, who is performing the research under the mentorship of Christopher Gayer and Mark Frey at Childrens Hospital Los Angeles (CHLA). Im deeply appreciative of the benefactors and the selection committee for awarding me the Broad Clinical Fellowship, as it is allowing me devoted time to focus on this important project, and to become a more well-rounded physician through this academic pursuit.

Brittany Rocque, a resident physician in general surgery, will use her fellowship to seek better ways to predict, detect and diagnose immune rejection in patients who have undergone liver transplantation. Nearly 60 percent of pediatric patients and at least 15 percent of adult patients reject their liver transplants, and this can currently only be confirmed through an invasive surgical biopsy. Rocque is utilizing the technology Imaging Mass Cytometry to identify and analyze the types of immune cells involved in rejection.

My project has the potential to provide a noninvasive option to assess rejection in transplanted patients, and to expand our understanding of immune rejection, said Rocque, who is being co-mentored by Juliet Emamaullee and Shahab Asgharzadeh at CHLA. Im greatly looking forward to applying my passion for transplantation surgery in the context of basic science, and enhancing my appreciation for the nuances of research, thanks to the Broad Clinical Research Fellowship.

A hematology-oncology fellow who will be transitioning to a junior faculty position at USC next year, Caitlin ONeill will study a condition known as clonal hematopoiesis or CH, a phenomenon common in the aging population. CH involves genetic mutations that cause the expansion of a particular population of blood cells without leukemia or related malignancies. CH increases risks for certain health conditions including heart disease.

During her Broad Clinical Research Fellowship, ONeill will look at one mutation seen in patients with CH: a mutation to the gene called Tet methylcytosine dioxygenase 2, or TET2. ONeill will explore if this mutation promotes blood clots, inflammation and heart disease.

The goal is to inform therapies to prevent heart disease and leukemic progression in aging patients with CH, said ONeill, who is working with co-mentors Casey OConnell and Rong Lu at USC. Im very happy to be working on this project, with support from the Broad Clinical Research Fellowship, during my transition to becoming a faculty member at USC.

More:
Broad Foundation brings together stem cell scientists, engineers and physicians at University of Southern - Mirage News

According to the World Health Organization (WHO), cardiovascular disease, specifically ischemic heart disease, is one of the leading causes of death worldwide. Cardiovascular diseases result in an estimated 17.9 million deaths each year. This is about 31% of all deaths worldwide (1). Medical researchers are continually working on ways to reduce those numbers, including the development of new technologies to combat premature deaths from cardiovascular diseases. This article will focus, in particular, on the value of induced pluripotent stem cells (iPSCs) in cardiac research.

iPSCs are a type of pluripotent stem cell. These are master cells that can differentiate into any cell or tissue the body needs. They are generated directly from somatic cells through ectopic expression of various transcription factors, such as

Theyve become key tools to model biological processes, particularly in cell types that are difficult to access from living donors. Many research laboratories are working to enhance reprogramming efficiency by testing different cocktails of transcription factors.

iPSCs have become essential in a number of different research fields, including cardiac research.

They are a valuable and advantageous technologic development for two main reasons:

Most people have heard of embryonic stem cells, which are one variation of pluripotent cells. Like iPSCs, they can be used to replace or restore tissues that have been damaged.

The problem is that embryonic stem cells are only found in preimplantation stage embryos (3). Whereas iPSCs are adult cells that have been genetically modified to work like embryonic stem cells. Thus, the term, inducedpluripotent stem cells.

The development of iPSCs was helpful because embryos are not needed. This reduces the controversy surrounding the creation and use of stem cells. Further, iPSCs from human donors are also more compatible with patients than animal iPSCs, making them even closer to their embryonic cousins.

The Japanese inventor of iPSCs, Professor Shinya Yamanaka earned a Nobel Prize in 2012 for the discovery that mature cells can be reprogrammed to become pluripotent. (4) The Prize was awarded to Dr. Yamanaka because of the significant medical and research implications this technology holds.

iPSCs hold a lot of promise for transplantation medicine. Further, they are highly useful in drug development and modeling of diseases.

iPSCs may become important in transplantation medicine because the tissues developed from them are a nearly identical match to the cell donors. This can potentially reduce the chances of rejection by the immune system (5).

In the future, and with enough research, it is highly possible that researchers may be able to perfect the iPSC technology so that it can efficiently reprogram cells and repair damaged tissues throughout the body.

iPSCs forgo the need for embryos and can be made to match specific patients. This makes them extremely useful in both research and medicine.

Every individual with damaged or diseased tissues could have their own pluripotent stem cells created to replace or repair them. Of course, more research is needed before that becomes a reality. To date, the use of iPSCs in therapeutic transplants has been very limited.

One of the most significant areas where iPSCs are currently being used is in cardiac research. With appropriate nutrients and inducers, iPSC can be programmed to differentiate into any cell type of the body, including cardiomyocyte. This heart-specific cell can then serve as a great model for therapeutic drug screening or assay development.

Another notable application of iPSCs in cardiac research is optical mapping technology. Optical mapping technology employs high-speed cameras and fluorescence microscopy to examines the etiology and therapy of cardiac arrhythmias in a patient-like environment. This is typically done by looking into electrical properties of multicellular cardiac preparations., e.g. action potential or calcium transient, at high spatiotemporal resolution (6).

Optical mapping technology can correctly record or acquire data from iPSCs. iPSCs are also useful in mimicking a patients cardiomyocytes with their specific behaviors, resulting in more reliable and quality data of cardiac diseases.

iPSCs are vital tools in cardiac research for the following reasons:

iPSCs are patient-specific because they are 100% genetically identical with their donors. This genomic make-up allows researchers to study patients pathology further and develop therapeutic agents for treating their cardiac diseases.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), help researchers predict the cardiotoxicity of drugs like with widely used chemotherapy reagents (10). Predictions like this were close to impossible before iPSC technology entered the research game.

iPSCs really come into play with their ability to model diseases. Because iPSCs are genetic matches to their living donors, they are uniquely useful for the study of genetic cardiac diseases like monogenic disorders. iPSCs help researchers understand how disease genotypes at the genetic level manifest as phenotypes at the cellular level (5).

Long QT syndrome, a condition that affects the repolarization of a patients heart after a heartbeat, is a notable example of iPSC-based disease modeling (7). This syndrome has been successfully modeled using iPSCs and is an excellent model for other promising target diseases (7).

Long QT syndrome is not the only disease that has been modeled by iPSCs. Other cardiac diseases like Barth syndrome-associated cardiomyopathy and drug-induced kidney glomerular injuries have been modeled as well (8).

The advent of iPSC technology has created a wealth of new opportunities and applications in cardiovascular research and treatments. In the near future, researchers hope that iPSC-derived therapies will be an option for thousands, if not millions of patients worldwide.

Original post:
What is the Value of iPSC Technology in Cardiac... - The Doctor Weighs In

Thursday, May 7, 2020, 8:30 a.m. EDT

NEW YORK, April 29, 2020 (GLOBE NEWSWIRE) -- BrainStorm-Cell Therapeutics Inc.(NASDAQ: BCLI), a leader in developing innovative autologous cellular therapies for highly debilitating neurodegenerative diseases, announced today, that the Company will hold a conference call to update shareholders on financial results for the first quarter endedMarch 31, 2020, and provide a corporate update, at 8:30 a.m, Eastern Daylight Time, onThursday, May 7, 2020.

BrainStorms CEO,Chaim Lebovits, will present a corporate update, after which, participant questions will be answered. Joining Mr. Lebovits to answer investment community questions will beRalph Kern, MD, MHSc, President and Chief Medical Officer, David Setboun, PhD, MBA, Executive Vice President and Chief Operating Officer andPreetam Shah, PhD, MBA, Executive Vice President and Chief Financial Officer.

Participants are encouraged to submit their questions prior to the call by sending them to:q@brainstorm-cell.com. Questions should be submitted by5:00 p.m. EDT, Tuesday, May 5, 2020.

Teleconference Details BRAINSTORM CELL THERAPEUTICS 1Q 2020

The investment community may participate in the conference call by dialing the following numbers:

Those interested in listening to the conference call live via the internet may do so by visiting the "Investors & Media" page of BrainStorm's website at http://www.ir.brainstorm-cell.com and clicking on the conference call link.

Those that wish to listen to the replay of the conference call can do so by dialing the numbers below. The replay will be available for 14 days.

ABOUT NUROWNNurOwn (autologous MSC-NTF cells) represent a promising investigational approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

ABOUT BRAINSTORM CELL THERAPEUTICS INC.:BrainStorm Cell Therapeutics Inc.is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwnCellular Therapeutic Technology Platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement as well as through its own patents, patent applications and proprietary know-how. Autologous MSC-NTF cells have received Orphan Drug status designation from theU.S. Food and Drug Administration(U.S.FDA) and theEuropean Medicines Agency(EMA) in ALS. BrainStorm has fully enrolled the Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in theU.S., supported by a grant from theCalifornia Institute for Regenerative Medicine(CIRM CLIN2-0989). The pivotal study is intended to support a BLA filing for U.S.FDAapproval of autologous MSC-NTF cells in ALS. BrainStorm received U.S.FDAclearance to initiate a Phase 2 open-label multi-center trial of repeat intrathecal dosing of MSC-NTF cells in Progressive Multiple Sclerosis (NCT03799718) inDecember 2018and has been enrolling clinical trial participants sinceMarch 2019. For more information, visit the company'swebsite.

SAFE HARBOR STATEMENT:Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could causeBrainStorm Cell Therapeutics Inc.'sactual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available athttp://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

Story continues

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BrainStorm-Cell Therapeutics to Announce First Quarter Financial Results and Provide a Corporate Update - Yahoo Finance

Cryopreservation has become an indispensable step in the daily routine of scientific research as well as in a number of medical applications, ranging from assisted reproduction and transplantations to cell-based therapies and biomarker identification. It is hardly possible to picture todays scientific and medical advancements without this technique.The successful development and implementation of all the therapeutic and scientific discoveries involving cryopreservation relies on the correct and safe translation of the method from the laboratory to the clinical and manufacturing scale.

With the need to correctly use this technique, more research is focusing on optimizing cryopreservation methods and investigating what the long-term effects and consequences are on the physiology of the cryopreserved material.

An important part of cell therapy research is focused on adult stem cells (ASCs). ASCs can be derived from different sources such as peripheral blood, bone marrow or adipose tissue and display strong promises because of their capacity to differentiate into any cell type of the human body.In recent work3, the team of Michael Pepper at the Institute for Cellular and Molecular Medicine in Pretoria, South Africa, explored the effects of cryopreservation on the differentiation ability of adipose tissue-derived stem cells (ADSCs). After analyzing gene expression of key adipogenic genes and the degree of differentiating cells, characterized with high levels of CD36 and intracellular lipid droplets, the scientists reported that slow freeze cryopreservation of cells shortly after their isolation causes no alterations on their ability to differentiate. Pepper is convinced of the necessity to perform such analysis when cryopreserving important cell pools: It is critical to do a post-thaw analysis of cell function to determine how the cryopreservation may have affected the cells.His team is analyzing the effects of cryopreservation on other cell types largely used in cell-based therapies such as hematological stem cells and peripheral blood mononuclear cells (PBMCs). Although they didnt observe major alterations in terms of immunophenotyping or the post-thaw proliferation of the cells, Pepper expresses his concern that more subtle characteristics might be affected.

Correct cryopreservation of cells intended for therapeutic use is crucial. This is very important particularly as cells may persist for a long time in the recipient. This area of cell therapy research definitely requires more attention, Pepper says. Moreover, his words reflect on the need to evaluate not only the direct post-thaw recovery, but to look deeper into the late-onset effects cryopreservation might have and ensure that transplanted cells have preserved their therapeutic properties.

In contrast to slow freezing, vitrification relies on the fast freezing of the material by putting it in high concentration of cryoprotectant and in contact with liquid nitrogen. This method allows the direct transition of water from liquid to solid state without crystal formation. The highly concentrated cryoprotectant prevents ice formation and therefore there is no need for slow cooling.

Although vitrification has a great potential, there are a couple of parameters that are a point of concern. The quick and drastic freeze is possible thanks to the high concentration of cryoprotectant, but the latter is also associated with higher toxicity. In some cases, an additional limitation is the direct contact of the sample with liquid nitrogen which is a predisposition for viral or bacterial contamination.The team of Christiani Amorim at the Institute for Experimental and Clinical Research in Louvain, Belgium, is approaching the challenges of vitrification in the context of ovarian auto-transplantation. Ovarian auto-transplantation consists of preserving a piece of ovarian tissue with active follicles from the pre-therapeutic ovary of a cancer patient, as chemotherapy often has damaging effects on the reproductive organs. This tissue sample will be conserved and auto-transplanted onto the patients ovary when she has recovered and wishes to become pregnant.In their recent research4, the authors used stepped vitrification, in which the concentration of the cryoprotectant is gradually increased while simultaneously temperature decreases. This avoids ice crystal formation and also prevents cryoprotectant toxicity.Although stepped vitrification has previously given good results in bovine ovarian tissue5, this was not the case for human ovarian tissue. The scientists didnt detect normal follicles following thawing and linked this to high cryoprotectant toxicity. Indeed, they observed all signs of dimethyl sulfoxide (DMSO)-related cell membrane damage: significant organelle damage, cell membrane disintegration and apoptosis. These observations imply on the variability of outcomes that the method could give when applied to the same type of tissue but from a different organism.Amorim is positive about the future of their method and recognizes the need for further research on the topic: I can see a great potential in the stepped vitrification approach, but I also believe that there is a lot we still need to learn before thinking about using it as method of choice for human ovarian tissue cryopreservation. The high cryoprotectant concentration that should be applied in this approach is my first concern. () Our study clearly showed that 50% DMSO is too high, so we need to try lower concentrations or combine it with other cryoprotectants.

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Freezing Life: The Current Trends in Cryopreservation - Technology Networks

NEW YORK, April 29, 2020 (GLOBE NEWSWIRE) -- BrainStorm-Cell Therapeutics Inc. (NASDAQ: BCLI), a leader in developing innovative autologous cellular therapies for highly debilitating neurodegenerative diseases, announced today, that the Company will hold a conference call to update shareholders on financial results for the first quarter ended March 31, 2020, and provide a corporate update, at 8:30 a.m, Eastern Daylight Time, on Thursday, May 7, 2020.

BrainStorms CEO, Chaim Lebovits, will present a corporate update, after which, participant questions will be answered. Joining Mr. Lebovits to answer investment community questions will be Ralph Kern, MD, MHSc, President and Chief Medical Officer, David Setboun, PhD, MBA, Executive Vice President and Chief Operating Officer and Preetam Shah, PhD, MBA, Executive Vice President and Chief Financial Officer.

Participants are encouraged to submit their questions prior to the call by sending them to: q@brainstorm-cell.com. Questions should be submitted by 5:00 p.m. EDT, Tuesday, May 5, 2020.

Teleconference Details BRAINSTORM CELL THERAPEUTICS 1Q 2020

The investment community may participate in the conference call by dialing the following numbers:

Those interested in listening to the conference call live via the internet may do so by visiting the "Investors & Media" page of BrainStorm's website at http://www.ir.brainstorm-cell.com and clicking on the conference call link.

Those that wish to listen to the replay of the conference call can do so by dialing the numbers below. The replay will be available for 14 days.

ABOUT NUROWNNurOwn (autologous MSC-NTF cells) represent a promising investigational approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors. Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. NurOwn is currently being evaluated in a Phase 3 ALS randomized placebo-controlled trial and in a Phase 2 open-label multicenter trial in Progressive MS.

ABOUT BRAINSTORM CELL THERAPEUTICS INC.:BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn Cellular Therapeutic Technology Platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement as well as through its own patents, patent applications and proprietary know-how. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (U.S. FDA) and the European Medicines Agency (EMA) in ALS. BrainStorm has fully enrolled the Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six sites in the U.S., supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a BLA filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm received U.S. FDA clearance to initiate a Phase 2 open-label multi-center trial of repeat intrathecal dosing of MSC-NTF cells in Progressive Multiple Sclerosis (NCT03799718) in December 2018 and has been enrolling clinical trial participants since March 2019. For more information, visit the company's website.

SAFE HARBOR STATEMENT:Statements in this announcement other than historical data and information, including statements regarding future clinical trial enrollment and data, constitute "forward-looking statements" and involve risks and uncertainties that could cause BrainStorm Cell Therapeutics Inc.'s actual results to differ materially from those stated or implied by such forward-looking statements. Terms and phrases such as "may", "should", "would", "could", "will", "expect", "likely", "believe", "plan", "estimate", "predict", "potential", and similar terms and phrases are intended to identify these forward-looking statements. The potential risks and uncertainties include, without limitation, BrainStorms need to raise additional capital, BrainStorms ability to continue as a going concern, regulatory approval of BrainStorms NurOwn treatment candidate, the success of BrainStorms product development programs and research, regulatory and personnel issues, development of a global market for our services, the ability to secure and maintain research institutions to conduct our clinical trials, the ability to generate significant revenue, the ability of BrainStorms NurOwn treatment candidate to achieve broad acceptance as a treatment option for ALS or other neurodegenerative diseases, BrainStorms ability to manufacture and commercialize the NurOwn treatment candidate, obtaining patents that provide meaningful protection, competition and market developments, BrainStorms ability to protect our intellectual property from infringement by third parties, heath reform legislation, demand for our services, currency exchange rates and product liability claims and litigation,; and other factors detailed in BrainStorm's annual report on Form 10-K and quarterly reports on Form 10-Q available at http://www.sec.gov. These factors should be considered carefully, and readers should not place undue reliance on BrainStorm's forward-looking statements. The forward-looking statements contained in this press release are based on the beliefs, expectations and opinions of management as of the date of this press release. We do not assume any obligation to update forward-looking statements to reflect actual results or assumptions if circumstances or management's beliefs, expectations or opinions should change, unless otherwise required by law. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance or achievements.

CONTACTSInvestor Relations:Preetam Shah, MBA, PhDChief Financial OfficerBrainStorm Cell Therapeutics Inc.Phone: + 1.862.397.1860pshah@brainstorm-cell.com

Media:Sean LeousWestwicke/ICR PRPhone: +1.646.677.1839sean.leous@icrinc.com

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BrainStorm-Cell Therapeutics to Announce First Quarter Financial Results and Provide a Corporate UpdateThursday, May 7, 2020, 8:30 am EDT - BioSpace

DURHAM, N.C., April 29, 2020 (GLOBE NEWSWIRE) -- Chimerix (NASDAQ:CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, today announced the Companys initiation of a Phase 2/3 study of dociparstat sodium (DSTAT) in COVID-19 patients with acute lung injury (ALI).

DSTAT is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, including the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding complications compared to commercially available forms of heparin.1

Given the severity of the COVID-19 pandemic, we have evaluated many potential targets to address the clinical manifestations associated with severe COVID-19,said Joseph Lasky, M.D., Professor of Medicine, Pulmonary and Critical Care Section Chief, John W. Deming, M.D. Endowed Chair in Internal Medicine at Tulane University Medical School. Based on the literature, we believe DSTAT has the potential to reduce the excessive inflammation, immune cell infiltration and hypercoagulation associated with poor outcomes in patients with severe COVID-19 infection.

DSTAT is well-suited to unlock the anti-inflammatory properties of heparin as it may be dosed at much higher levels than any available form of heparin without triggering bleeding complications, said Mike Sherman, Chief Executive Officer of Chimerix. We had planned to evaluate DSTAT in several indications of high unmet need, including ALI from different causes. The pandemic intensified our focus on ALI associated with COVID-19. Our team has worked closely with critical care physicians treating COVID-19 patients and with the U.S. Food and Drug Administration (FDA) to develop a Phase 2/3 protocol to determine if DSTAT can reduce the need for mechanical ventilation and improve the rate of survival in patients with severe COVID-19 infection.

Phase 2/3 Study Design

The study is a 1:1 randomized, double-blind, placebo-controlled, Phase 2/3 trial to determine the safety and efficacy of DSTAT in adults with severe COVID-19 who are at high risk of respiratory failure. Eligible subjects will be those with confirmed COVID-19 who require hospitalization and supplemental oxygen therapy. The primary endpoint of the study is the proportion of subjects who survive and do not require mechanical ventilation through day 28. Additional endpoints include time to improvement as assessed by the National Institute of Allergy and Infectious Disease ordinal scale, time to hospital discharge, time to resolution of fever, number of ventilator-free days, all-cause mortality, and changes in key biomarkers (e.g. interleukin-6 (IL-6), tumor necrosis factor- (TNF-), high mobility group box 1 (HMGB1), C-reactive protein and d-dimer).

The Phase 2 portion of the study will enroll 24 subjects to confirm the maximum safe dose and will then expand by an additional 50 patients (74 total) at the selected dose. A formal analysis of all endpoints, including supportive biomarkers will be performed at the conclusion of the phase 2 portion of the study. Contingent upon positive results, the Phase 3 portion of the study will enroll approximately 450 subjects.

Clinical Rationale for DSTAT in COVID-19 Patients with ALI

The clinical manifestations of COVID-19 range from mild, self-limited respiratory tract illness to severe alveolar damage and progressive respiratory failure, multiple organ failure, and death. Mortality in COVID-19 is associated with severe pulmonary disease and coagulation disorders such as disseminated intravascular coagulation (DIC).2,3

The mechanistic rationale supporting DSTATs potential in ALI patients with COVID-19 is two-fold:

In a recent Phase 2 Acute Myeloid Leukemia (AML) study DSTAT was well tolerated with adverse events similar across DSTAT and control groups. DSTAT is an investigational agent, not yet licensed or approved for use.

Conference Call and Webcast

Chimerix will host a conference call and live audio webcast today at 8:30 a.m. ET. To access the live conference call, please dial 877-354-4056 (domestic) or 678-809-1043 (international) at least five minutes prior to the start time and refer to conference ID 8263766.

A live audio webcast of the call will also be available on the Investors section of Chimerixs website, http://www.chimerix.com. An archived webcast will be available on the Chimerix website approximately two hours after the event.

About Chimerix

Chimerix is a development-stage biopharmaceutical company dedicated to accelerating the advancement of innovative medicines that make a meaningful impact in the lives of patients living with cancer and other serious diseases. Its two clinical-stage development programs are dociparstat sodium (DSTAT) and brincidofovir (BCV).

Dociparstat sodium is a potential first-in-class glycosaminoglycan compound derived from porcine heparin that has low anticoagulant activity In vitro and in vivo animal model data support DSTATs potential to reduce the inflammation and cellular infiltration associated with acute lung injury and address coagulation disorders associated with COVID-19 pathology. Separately, DSTAT inhibits the activities of several key proteins implicated in the viability of AML blasts and leukemic stem cells in the bone marrow during chemotherapy (e.g., CXCL12, selectins, HMGB1, elastase). Randomized Phase 2 data suggest that DSTAT may also accelerate platelet recovery post-chemotherapy via inhibition of PF4, a negative regulator of platelet production that impairs platelet recovery following chemotherapy. BCV is an antiviral drug candidate in development as a medical countermeasure for smallpox. For further information, please visit the Chimerix website, http://www.chimerix.com.

Forward Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks and uncertainties that could cause actual results to differ materially from those projected. Forward-looking statements include those relating to, among other things, the mechanism of action of DSTAT and its potential in ALI patients with COVID-19; Chimerixs ability to develop DSTAT, including the initiation of a Phase 2/3 clinical trial for DSTAT as a potential treatment for ALI associated with COVID-19; and Chimerixs ability to submit and/or obtain regulatory approvals for DSTAT. Among the factors and risks that could cause actual results to differ materially from those indicated in the forward-looking statements are risks that DSTAT may not achieve the endpoints of the Phase 2/3 clinical trial; risks that DSTAT may not obtain regulatory approval from the FDA or such approval may be delayed or conditioned; risks that development activities related to DSTAT may not be completed on time or at all; Chimerixs reliance on a sole source third-party manufacturer for drug supply; risks that ongoing or future trials may not be successful or replicate previous trial results, or may not be predictive of real-world results or of results in subsequent trials; risks and uncertainties relating to competitive products and technological changes that may limit demand for our drugs; risks that our drugs may be precluded from commercialization by the proprietary rights of third parties; and additional risks set forth in the Company's filings with the Securities and Exchange Commission. These forward-looking statements represent the Company's judgment as of the date of this release. The Company disclaims, however, any intent or obligation to update these forward-looking statements.

CONTACT:Investor Relations:Michelle LaSpaluto919 972-7115ir@chimerix.com

Will OConnorStern Investor Relationswill@sternir.com212-362-1200

Media:David SchullRusso Partners858-717-2310david.schull@russopartnersllc.com

note: DSTAT may be referred to as 2-O,3-O desulfated heparin, ODSH or CX-01 in these references.

Excerpt from:
Chimerix Announces Initiation of a Phase 2/3 Study of DSTAT in Acute Lung Injury for Patients with Severe COVID-19 - BioSpace

CRANFORD, N.J., April 27, 2020 /PRNewswire/ --Citius Pharmaceuticals, Inc.. ("Citius" or the "Company") (Nasdaq: CTXR), a specialty pharmaceutical company focused on developing and commercializing critical care drug products, today announced that it submitted a pre-IND meeting request and supporting briefing documents to the Center for Biologics Evaluation and Research ("CBER") of the FDA under the Coronavirus Treatment Acceleration Program (CTAP) on April 24. The Company has requested the Division's feedback to support the most expeditious pathway into the clinic to evaluate a novel cell therapy in patients suffering from COVID-19-related ARDS.

The cells, called NoveCite Cells or NC-MSCs, are made by Novellus, Inc. ("Novellus"), a Cambridge-based biotechnology company, using its patented mRNA-based cell-reprogramming process. NC-MSCs are mesenchymal stem cells derived from a single donor's fibroblasts that have been dedifferentiated into an induced pluripotent stem cell (iPSC) master cell bank, thereby avoiding the need to source additional donor cells. The iPSCs are then further differentiated into a mesenchymal stem cell (MSC) therapy. Citius and Novellus plan to develop NC-MSCs for the treatment of ARDS, and last month the companies signed an exclusive option agreement.

The Company plans a multi-center randomized placebo-controlled dose-finding study followed by an expansion phase to assess the safety, tolerability, and efficacy of NC-MSCs in patients with moderate to severe ARDS due to COVID-19. The proposed trial, a Phase 1b/2 clinical trial, is titled "A Randomized Placebo-Controlled Dose-Finding Study Followed by a Dose Level Expansion to Assess the Safety and Efficacy of NoveCite MSCs in Subjects with Acute Respiratory Distress Syndrome (ARDS) Due to SARS-CoV-2 Disease (COVID-19)," or "MARCO". The primary objectives of this study are to evaluate the safety and efficacy of NoveCite cells as a treatment for subjects with moderate-to-severe ARDS due to COVID-19 and to identify therapeutic doses.

"MSCs have an established track-record of clinical safety, and have shown promise in the treatment of inflammatory lung disease," said Matt Angel, PhD, co-founder and Chief Science Officer at Novellus, Inc. "Our research has shown that the NoveCite cells, being derived from mRNA-reprogrammed iPSCs, secrete higher levels of immunomodulatory proteins than donor-derived MSCs, and have unique manufacturing advantages."

"We believe we have the key elements in place from a clinical design and manufacturing point of view to evaluate this novel cell therapy approach to deal with the current pandemic," said Myron Holubiak, Chief Executive Officer of Citius. "ARDS is a very serious complication for many patients suffering from COVID-19, and is believed to account for about 80% of the deaths in ventilated patients. There is no proven or FDA-approved treatment for it, other than oxygen therapy, including use of mechanical ventilation, and fluid management. Literature from previous investigational studies with MSCs in the treatment of lung injuries support the idea that MSCs could prove effective in treating COVID-19-related ARDS. We look forward to our FDA discussions and are excited to be at the cusp of what could be a novel and effective therapy for ARDS."

About Acute Respiratory Distress Syndrome (ARDS)ARDS is a type of respiratory failure characterized by rapid onset of widespread inflammation in the lungs. ARDS is a rapidly progressive disease that occurs in critically ill patients most notably now in those diagnosed with COVID-19. ARDS affects approximately 200,000 patients per year in the U.S., exclusive of the current COVID-19 pandemic, and has a 30% to 50% mortality rate. ARDS is sometimes initially diagnosed as pneumonia or pulmonary edema (fluid in the lungs from heart disease). Symptoms of ARDS include shortness of breath, rapid breathing and heart rate, chest pain (particularly while inhaling), and bluish skin coloration. Among those who survive ARDS, a decreased quality of life is relatively common.

About Coronavirus Treatment Acceleration Program (CTAP)In response to the pandemic, the FDA has created an emergency program called the Coronavirus Treatment Acceleration Program (CTAP) to accelerate the development of treatments for COVID-19. By redeploying staff, the FDA is responding to COVID-19-related requests and reviewing protocols within 24 hours of receipt. The FDA said CTAP "uses every available method to move new treatments to patients as quickly as possible, while at the same time finding out whether they are helpful or harmful." In practice, that means developers of potential treatments for COVID-19 will benefit from an unusually faster track at the FDA to shorten wait times at multiple steps of the process.

About Citius Pharmaceuticals, Inc.Citius is a late-stage specialty pharmaceutical company dedicated to the development and commercialization of critical care products, with a focus on anti-infectives and cancer care. For more information, please visit http://www.citiuspharma.com.

About Novellus, Inc.Novellus is a pre-clinical stage biotechnology company developing engineered cellular medicines using its non-immunogenic mRNA, nucleic-acid delivery, gene editing, and cell reprogramming technologies. Novellus is privately held and is headquartered in Cambridge, MA. For more information, please visit http://www.novellus-inc.com.

Safe HarborThis press release may contain "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Such statements are made based on our expectations and beliefs concerning future events impacting Citius. You can identify these statements by the fact that they use words such as "will," "anticipate," "estimate," "expect," "should," and "may" and other words and terms of similar meaning or use of future dates. Forward-looking statements are based on management's current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition, and stock price. Factors that could cause actual results to differ materially from those currently anticipated are: the risk of successfully negotiating a license agreement with Novellus within the option period; our need for substantial additional funds; the ability to access the FDA's CTAP program for the MARCO trial; the estimated markets for our product candidates, including those for ARDS, and the acceptance thereof by any market; risks associated with conducting trials for our product candidates, including those expected to be required for any treatment for ARDS and our Phase III trial for Mino-Lok; risks relating to the results of research and development activities; risks associated with developing our product candidates, including any licensed from Novellus, including that preclinical results may not be predictive of clinical results and our ability to file an IND for such candidates; uncertainties relating to preclinical and clinical testing; the early stage of products under development; risks related to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; our ability to identify, acquire, close, and integrate product candidates and companies successfully and on a timely basis; our ability to attract, integrate, and retain key personnel; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions, or circumstances on which any such statement is based, except as required by law.

Contact:Andrew ScottVice President, Corporate Development(O) 908-967-6677 x105ascott@citiuspharma.com

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SOURCE Citius Pharmaceuticals, Inc.

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Citius Announces Pre-IND Submission to FDA Under the Coronavirus Treatment Acceleration Program for a Novel Stem Cell Therapy for Acute Respiratory...

Astrocytes play a direct role in the regulation of neuronal circuits involved in learning and memory, according to new research from Baylor College of Medicine and M.D. Anderson Cancer Center.

Huang et al reveal region-specific transcriptional dependencies for astrocytes and identify astrocytic NFIA as a key transcriptional regulator of hippocampal circuits. Image credit: Huang et al, doi: 10.1016/j.neuron.2020.03.025.

Astrocytes are star-shaped glial cells in the brain and spinal cord.

They have unique cellular, molecular and functional properties and outnumber neurons by over fivefold. They occupy distinct brain regions, indicating regional specialization.

There is evidence suggesting that transcription factors proteins involved in controlling gene expression regulate astrocyte diversity.

A team led by Professor Benjamin Deneen from Baylor College of Medicine looked to get a better understanding of the role transcription factor NFIA, a known regulator of astrocyte development, played in adult mouse brain functions.

The researchers worked with a mouse model they had genetically engineered to lack the NFIA gene specifically in adult astrocytes in the entire brain.

They analyzed several brain regions, looking for alterations in astrocyte morphology, physiology and gene expression signatures.

We found that NFIA-deficient astrocytes presented defective shapes and altered functions, Professor Deneen said.

Surprisingly, although the NFIA gene was eliminated in all brain regions, only the astrocytes in the hippocampus were severely altered. Other regions, such as the cortex and the brain stem, were not affected.

Astrocytes in the hippocampus also had less calcium activity calcium is an indicator of astrocyte function as well as a reduced ability to detect neurotransmitters released from neurons.

NFIA-deficient astrocytes also were not as closely associated with neurons as normal astrocytes.

Importantly, all these morphological and functional alterations were linked to defects in the animals ability to learn and remember, providing the first evidence that astrocytes are to some extent controlling the neuronal circuits that mediate learning and memory.

Astrocytes in the brain are physically close to and communicate with neurons. Neurons release molecules that astrocytes can detect and respond to, Professor Deneen said.

We propose that NFIA-deficient astrocytes are not able to listen to neurons as well as normal astrocytes, and, therefore, they cannot respond appropriately by providing the support needed for efficient memory circuit function and neuronal transmission. Consequently, the circuit is disrupted, leading to impaired learning and memory.

The findings were published online in the journal Neuron.

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Anna Yu-Szu Huang et al. Region-Specific Transcriptional Control of Astrocyte Function Oversees Local Circuit Activities. Neuron, published online April 21, 2020; doi: 10.1016/j.neuron.2020.03.025

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Study Reveals New Role of Astrocytes in Brain Function | Neuroscience - Sci-News.com

Central to a lot of scientific research into aging are tiny caps on the ends of our chromosomes called telomeres. These protective sequences of DNA grow a little shorter each time a cell divides, but by intervening in this process, researchers hope to one day regulate the process of aging and the ill health effects it can bring. A Harvard team is now offering an exciting pathway forward, discovering a set of small molecules capable of restoring telomere length in mice.

Telomeres can be thought of like the plastic tips on the end of our shoelaces, preventing the fraying of the DNA code of the genome and playing an important part in a healthy aging process. But each time a cell divides, they grow a little shorter. This sequence repeats over and over until the cell can no longer divide and dies.

This process is linked to aging and disease, including a rare genetic disease called dyskeratosis congenita (DC). This is caused by the premature aging of cells and is where the Harvard University team focused its attention, hoping to offer alternatives to the current treatment that involves high-risk bone marrow transplants and which offers limited benefits.

One of the ways dyskeratosis congenita comes about is through genetic mutations that disrupt an enzyme called telomerase, which is key to maintaining the structural integrity of the telomere caps. For this reason, researchers have been working to target telomerase for decades, in hopes of finding ways to slow or even reverse the effects of aging and diseases like dyskeratosis congenita.

Once human telomerase was identified, there were lots of biotech startups, lots of investment, says Boston Childrens Hospital's Suneet Agarwal, senior investigator on the new study. But it didnt pan out. There are no drugs on the market, and companies have come and gone.

Agarwal has been studying the biology of telomerase for the past decade, and back in 2015 he and his team discovered a gene called PARN that plays a role in the action of the telomerase enzyme. This gene normally processes and stabilizes an important component of telomerase called TERC, but when it mutates, it results in less of the enzyme being produced and, in turn, the telomeres becoming shortened prematurely.

For the new study, Harvard researchers screened more than 100,000 known chemicals in search of compounds that could preserve healthy function of PARN. This led them to small handful that seemed capable of doing so by inhibiting an enzyme called PAPD5, which serves to unravel PARN and destabilize TERC.

We thought if we targeted PAPD5, we could protect TERC and restore the proper balance of telomerase, says Harvard Medical Schools Neha Nagpal, first author on the new paper.

These chemicals were tested on stem cells in the lab, made from the cells of patients with dyskeratosis congenita. These compounds boosted TERC levels in those stem cells and restored telomeres to their normal length. However, rather than a scattergun approach, the team really wanted to test for safety and see if the treatment could precisely target stem cells carrying the right ingredients for telomerase formation.

More specifically, the team wanted to see if this could be achieved by having the PAPD5-inhibiting drugs recognize and respond to another important component of telomerase, a molecule called TERT. To do so, in the next round of experiments the team used human blood stem cells and triggered mutations in the PARN gene that give rise to dyskeratosis congenita. These were then implanted into mice that were treated with the compounds, with the team finding the treatment boosted TERC, restored telomere length in the stem cells and had no ill effects on the rodents.

This provided the hope that this could become a clinical treatment, says Nagpal.

The team will now continue its work in an effort to prove these small molecules are a safe and effective way to apply the brakes to dyskeratosis congenita, other diseases, and possibly aging more broadly.

We envision these to be a new class of oral medicines that target stem cells throughout the body, Agarwal says. We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.

The research was published in the journal Cell Stem Cell.

Source: Boston Childrens Hospital via Harvard University

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Molecules identified that reverse cellular aging process - New Atlas

Capping decades of research, a new study may offer a breakthrough in treatingdyskeratosis congenitaand other so-called telomere diseases, in which cells age prematurely.

Using cells donated by patients with the disease, researchers at theDana-Farber/Boston Childrens Cancer and Blood Disorders Centeridentified several small molecules that appear to reverse this cellular aging process.Suneet Agarwal, the studys senior investigator, hopes at least one of these compounds will advance toward clinical trials. Findings werepublished Tuesday in the journal Cell Stem Cell.

If so, it could be the first treatment for dyskeratosis congenita, or DC, that could reverse all of the diseases varying effects on the body. The current treatment, bone marrow transplant, is high-risk, and only helps restore the blood system, whereas DC affects multiple organs.

The compounds identified in the study restore telomeres, protective caps on the tips of our chromosomes that regulate how our cells age. Telomeres consist of repeating sequences of DNA that get shorter each time a cell divides.

The bodys stem cells, which retain their youthful qualities, normally make an enzyme called telomerase that builds telomeres back up again. But when telomeres cant be maintained, tissues age before their time. A spectrum of diseases can result not just DC, but also aplastic anemia, liver cirrhosis, and pulmonary fibrosis.

The discovery of telomerase 35 years ago, earninga Nobel Prize in 2009, galvanized the scientific world. Subsequent studies suggested the enzyme could be a key to reversing aging, as well as treating cancer, in which malignant cells become immortal and divide indefinitely.

For years, researchers have tried to find a simple and safe way to manipulate telomerase, preserve telomeres, and create cures for telomere diseases.

Once human telomerase was identified, there were lots of biotech startups, lots of investment, says Agarwal, who has researched the biology of telomerase for the past decade. But it didnt pan out. There are no drugs on the market, and companies have come and gone.

DC can be caused by mutations in any of multiple genes. Most of these mutations disrupt telomerase formation or function in particular, by disrupting two molecules called TERT and TERC that join together to form telomerase. TERT is an enzyme made in stem cells, and TERC is a so-called non-coding RNA that acts as a template to create telomeres repeating DNA sequences. Both TERT and TERC are affected by a web of other genes that tune telomerases action.

One of these genes is PARN. In 2015, Agarwal and colleagues showed inNatureGeneticsthat PARN is important for processing and stabilizing TERC. Mutations in PARN mean less TERC, less telomerase, and prematurely shortened telomeres.

Thenew study, led by Harvard Medical School postdoctoral fellow Neha Nagpal, delved further, focusing on an enzyme that opposes PARN and destabilizes TERC, called PAPD5.

We thought if we targeted PAPD5, we could protect TERC and restore the proper balance of telomerase, says Nagpal, first author on the paper.

Nagpal and her colleagues first conducted large-scale screening studies to identify PAPD5 inhibitors, testing more than 100,000 known chemicals. They got 480 initial hits, which they ultimately narrowed to a small handful.

They then tested the inhibitors in stem cells made from the Martins cells and those of other patients with DC. To the teams delight, the compounds boosted TERC levels in the cells and restored telomeres to their normal length.

But the real challenge was to see if the treatment would be safe and specific, affecting only the stem cells bearing TERT. To test this, the team introduced DC-causing PARN mutations into human blood stem cells, transplanted those cells into mice, then treated the mice with oral PAPD5 inhibitors. The compounds boosted TERC and restored telomere length in the transplanted stem cells, with no adverse effect on the mice or on the ability to form different kinds of blood cells.

This provided the hope that this could become a clinical treatment, says Nagpal.

In the future, Agarwal, Nagpal, and colleagues hope to validate PAPD5 inhibition for other diseases involving faulty maintenance of telomeres and perhaps even aging itself. They are most excited about two compounds, known as BCH001 and RG7834 that are under further development.

We envision these to be a new class of oral medicines that target stem cells throughout the body, Agarwal says. We expect restoring telomeres in stem cells will increase tissue regenerative capacity in the blood, lungs, and other organs affected in DC and other diseases.

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Breakthrough to halt premature aging of cells - ScienceBlog.com

A few weeks afterreceiving chimeric antigen receptor (CAR) T-cell (CAR-T) therapy, many patientsexperience prolonged reductions in blood cell counts, possibly making them morevulnerable to infections.

Two recent studies characterized the extent and duration of postCAR-T cytopenia among patients receiving CAR-T therapy for hematological malignancies with 1 study offering insights on some of the possible factors that may influence hematological count recovery.

Whats important to know is that by day 90, mostpatients recover, noted UroosaIbrahim, MD, stemcell transplantation and cellular therapy fellow at the Tisch Cancer Instituteof the Icahn School of Medicine at Mount Sinai,New York, who coauthored 1 of the studies. Were supporting them for [approximately]3 months [with treatment], but then theyll recover, which is good to know.

One study by MemorialSloan Kettering Cancer Center (MSKCC) researchers followed 83 adult patientswho received CAR-T therapy: 40 patients received 1 of 2 Food and DrugAdministration (FDA)-approved therapies, axicabtageneciloleucel (axi-cel; Yescarta) ortisagenlecleucel (tisa-cel; Kymriah), to treat relapsed/refractory B-cell lymphoma.

The remainder comprised 37 patients with relapsed/refractory B-cell acute lymphoblastic leukemia who were currently enrolled in a clinical trial in which they received an experimental CAR-T therapy where cells express the 19-28z CAR construct (ClinicalTrials.gov Identifier: NCT01044069), and 6 multiple myeloma patients who received a different experimental CAR-T construct that targets the B-cell maturation antigen (BCMA) (ClinicalTrials.gov Identifier: NCT03070327). The findings were presented at the annual Transplantation and Cellular Therapy Meetings of ASCT and CIBMTR in February 2020.1

By 1 month, theresearchers observed that 24% of patients experienced a complete recovery ofhemoglobin, platelets, absolute neutrophil count, and white blood cell counts recovery being defined as reaching safe levels, and without requiringtransfusions or treatment with growth factors.

Recovery of hemoglobinwas noted in 61% of patients, platelets in 51% of patients, absolute neutrophilcount in 33% of patients, and white blood cell count in 28% of patients.Examining 41 patients at 3 months, those figures were 93%, 90%, 81%, and 59%,respectively, and overall, 56% saw a complete blood count recovery.

The results werebroadly consistent with recent research by Dr Ibrahim and Keren Osman, MD,associate professor and director of medicine at the Icahn School of Medicine atMount Sinai and director of cellular therapy service in the bone marrow andstem cell transplantation program at the schools Tisch Cancer Institute. Thatstudy comprised 50 patients 41 with multiple myeloma and 9 with diffuse largeB-cell lymphoma who received either axicabtagene ciloleucel, or 1 of 2 experimentalanti-BCMA CAR-T therapies, bb2121 or bb21217.

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What Factors Influence Hematological Recovery in Patients Who Receive CAR-T Therapies? - Cancer Therapy Advisor

Mount Sinai Health System announced that they will be using remestemcel-L (Ryoncil), an innovative allogeneic stem cell therapy, in patients with coronavirus disease 2019 (COVID-19).

Additionally, Mount Sinai indicated that they will play a central role in a clinical trial for patients with severe acute respiratory distress syndrome, which affects individuals with severe cases of COVID-19.

Remestemcel-L has previously been tested in patients who have had a bone marrow transplant, who can experience an overactive immune response similar to that observed in severe cases of COVID-19.

Mount Sinai began administering remestemcel-L to patients in late March under the FDAs compassionate use program. The therapy was given to 10 patients with moderate to severe cases of COVID-19-related acute respiratory distress syndrome (ARDS), most of whom were on ventilators, and the doctors saw encouraging results.

We are encouraged by what we have seen so far and look forward to participating in the randomized controlled trial starting soon that would better indicate whether this is an effective therapy for patients in severe respiratory distress from COVID-19, Keren Osman, MD, medical director of the Cellular Therapy Service in the Bone Marrow and Stem Cell Transplantation Program at The Tisch Cancer Institute at Mount Sinai and associate professor of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai, said in a press release.

The randomized clinical trial evaluating the therapeutic benefit and safety of remestemcel-L will be conducted at Mount Sinai, which will serve as the clinical and data coordinating center. The stem cell therapy will be evaluated in 240 patients with COVID-19-related ARDS in the US and Canada. Moreover, the trial will be conducted as a public-private partnership between the Cardiothoracic Surgical Trials Network.

The coronavirus pandemic has caused exponential increases of people suffering with acute respiratory distress syndrome, requiring intubation and mechanical ventilation with many dying, Annetine Gelijns, PhD, the Edmond A. Guggenheim Professor of Health Policy at the Icahn School of Medicine at Mount Sinai, said in a press release. We have designed a clinical trial that will expeditiously determine whether the stem cell therapy will offer a life-saving therapy for a group of patients with a dismal prognosis.

Remestemcel-L consists of mesenchymal stem cells. The therapy was previously assessed in a phase III trial in children who had graft-versus-host disease (GVHD), which can occur after bone marrow transplants. Further, the inflammation that occurs in GVHD is the result of a cytokine storm. A similar cytokine storm has been found to take place in patients with COVID-19 who develop acute respiratory distress syndrome.

These stem cells have shown excellent response rates in severe graft-versus-host disease in children, John Levine, MD, professor of Hematology, Medical Oncology, and Pediatrics at the Icahn School of Medicine at Mount Sinai, who is also the co-director of the Mount Sinai Acute GVHD International Consortium (MAGIC), said in a press release. Mesenchymal stem cells have a natural property that dampens excessive immune responses.

Some institutions have also begun testing anti-IL-6 agents, such as tocilizumab (Actemra), for the treatment of cytokine release syndrome in patients with COVID-19 who develop acute respiratory distress syndrome.

Reference:

Mount Sinai Leading the Way in Innovative Stem Cell Therapy for COVID-19 Patients [news release]. New York, NY. Published April 9, 2020. newswise.com/coronavirus/mount-sinai-leading-the-way-in-innovative-stem-cell-therapy-for-covid-19-patients/?article_id=729684&sc=dwhr&xy=10019792. Accessed April 15, 2020.

See the article here:
Planned Clinical Trial of Allogeneic Stem Cell Therapy Remestemcel-L in Patients with COVID-19 - Cancer Network

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?"According to the , some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection."Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.Older adultsEight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.Inflammation in older adults can be more intense, leading to organ damage.Those with lung disease, asthma or heart conditionsPeople with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.The immunocompromisedAccording to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.Severe obesityPeople with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease."Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.DiabetesPeople with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.Kidney and liver diseaseThe kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.Neurodevelopmental conditionsNeurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.Staying safe when you're more at riskIf you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?

"According to the [Centers for Disease Control and Prevention], some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.

The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection.

"Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."

Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.

Eight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.

Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.

The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.

Inflammation in older adults can be more intense, leading to organ damage.

People with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.

COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.

According to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.

Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.

Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.

A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.

When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.

HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.

People with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease.

"Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.

People with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.

Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.

The kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.

The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.

Neurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.

These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.

People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.

Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.

If you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.

Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.

If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

More:
What are the underlying conditions causing more serious illness from coronavirus? - KSBW The Central Coast

-Spinal cord injury (SCI) creates a complex microenvironment that is not conducive to repair; growth factors are in short supply, whereas factors that inhibit regeneration are plentiful. In a new report, researchers have developed a structural bridge material that simultaneously stimulates IL-10 and NT-3 expression using a single bi-cistronic vector to alter the microenvironment and enhance repair. The article is reported in Tissue Engineering, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the article for free on the Tissue Engineering website through May 17, 2020.

In Polycistronic Delivery of IL-10 and NT-3 Promotes Oligodendrocyte Myelination and Functional Recovery in a Mouse Spinal Cord Injury Model, Lonnie D. Shea, PhD, University of Michigan, and coauthors report the development of a new poly(lactide-co-glycolide) (PLG) bridge with an incorporated polycistronic IL-3/NT-3 lentiviral construct. This material was used to stimulate repair in a mouse SCI model. IL-10 was included to successfully stimulate a regenerative phenotype in recruited macrophages, while NT-3 was used to promote axonal survival and elongation. The combined expression was successful; axonal density and myelination were increased, and locomotor functional recovery in mice was improved.

Inflammation plays a vital role in tissue repair and regeneration, and the use of a PLG bridge to take advantage of the inflammatory response to promote SCI repair is an elegant way to take advantage of these natural processes to improve SCI healing, says Tissue Engineering Co-Editor-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX.

About the Journal

Tissue Engineering is an authoritative peer-reviewed journal published monthly online and in print in three parts: Part A, the flagship journal published 24 times per year; Part B: Reviews, published bimonthly, and Part C: Methods, published 12 times per year. Led by Co-Editors-in-Chief Antonios G. Mikos, PhD, Louis Calder Professor at Rice University, Houston, TX, and John P. Fisher, PhD, Fischell Family Distinguished Professor & Department Chair, and Director of the NIH Center for Engineering Complex Tissues at the University of Maryland, the Journal brings together scientific and medical experts in the fields of biomedical engineering, material science, molecular and cellular biology, and genetic engineering. Leadership of Tissue Engineering Parts B (Reviews) and Part C (Methods) is provided by Katja Schenke-Layland, PhD, Eberhard Karls University, Tbingen, Heungsoo Shin, PhD, Hanyang University; and John A. Jansen, DDS, PhD, Radboud University, and Xiumei Wang, PhD, Tsinghua University respectively. Tissue Engineering is the official journal of the Tissue Engineering & Regenerative Medicine International Society (TERMIS). Complete tables of content and a sample issue may be viewed on the Tissue Engineering website.

About the Publisher

Mary Ann Liebert, Inc., publishers is a privately held, fully integrated media company known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research, including Stem Cells and Development, Human Gene Therapy, and Advances in Wound Care. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industrys most widely read publication worldwide. A complete list of the firms 90 journals, books, and newsmagazines is available on the e Mary Ann Liebert, Inc., publishers website.

Read the original:
Co-delivery of IL-10 and NT-3 to Enhance Spinal Cord Injury Repair - Mirage News

(CNN) Weve heard that elderly people and those with underlying health conditions are most at risk if theyre infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?

According to the [Centers for Disease Control and Prevention], some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment, said CNN Chief Medical Correspondent Dr. Sanjay Gupta in anepisode of CNNs Coronavirus: Fact vs. Fiction podcast. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.

The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection.

Think of it like this, Dr. Gupta suggested. In your everyday life, youre always fighting off pathogens. Most of the time you dont even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesnt have a preexisting illness.

Additionally, there are more specific reasons why each condition has its own vulnerabilities. Heres a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.

Eight out of 10 deaths reported in the US have been in adults ages 65 and older, according to theCDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.

Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according toJohns Hopkins Medicine.

The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as Covid-19 of important concern because of the potential for lung damage.

Inflammation in older adults can be more intense, leading to organ damage.

People with chronic airway and lung diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause,Johns Hopkins Medicine reported.

Covid-19 affects a persons airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.

According to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or otherimmune-weakening medicationscan also hamper a persons immune function.

Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according toCancer Research UK. Cancer prevents bone marrow from making enough blood cells.

Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.

A2017 studyfound cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.

When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease andmitigate the immune systems reactionby suppressing its function. After the operation, it takes time for your immune system to be up and running again.

HIV and AIDS attack the bodys immune system, specifically the bodys T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to theCDC.

People with severe obesity, or a body mass index of 40 or higher, are athigher risk of serious disease.

Obesity shares with most chronic diseases the presence of an inflammatory component, a2012 studysaid. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.

People with type 1 or type 2 diabetes face an increased risk of getting really sick with Covid-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according toDiabetes in Control, a news and information resource for medical professionals.

Higherlevels of inflammationhave been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.

The kidneysproduce several hormonesthat affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to theNational Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.

The liver is an integral member of the bodysline of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.

Neurological and neurodevelopmental conditions may also increase the risk of serious Covid-19 for people of any age.

These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to theCDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.

People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinsons, have been recognized to haveinflammatory components, which may harm the immune system.

Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with Covid-19.

If you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.

Stay home whenever possible and avoid close contact with people, theCDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.

If you dont have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

Click here for more coronavirus coverage.

The-CNN-Wire & 2020 Cable News Network, Inc., a WarnerMedia Company. All rights reserved.

Here is the original post:
What exactly are underlying conditions? And why people with them may experience more serious illness from coronavirus - Boston News, Weather, Sports |...

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?"According to the , some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection."Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.Older adultsEight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.Inflammation in older adults can be more intense, leading to organ damage.Those with lung disease, asthma or heart conditionsPeople with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.The immunocompromisedAccording to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.Severe obesityPeople with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease."Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.DiabetesPeople with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.Kidney and liver diseaseThe kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.Neurodevelopmental conditionsNeurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.Staying safe when you're more at riskIf you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

We've heard that elderly people and those with underlying health conditions are most at risk if they're infected with coronavirus, but those can seem like really general terms. Who does that include? And why can they face more serious illness?

"According to the [Centers for Disease Control and Prevention], some of the underlying conditions that may put you at higher risk include: chronic lung disease and asthma, heart disease and undergoing cancer treatment," said CNN Chief Medical Correspondent Dr. Sanjay Gupta. Anyone with diabetes, kidney failure or liver failure may also be at higher risk.

The role of the immune system is to protect against disease or other potentially damaging pathogens. A strong one is needed to help stave off coronavirus infection.

"Think of it like this," Dr. Gupta suggested. "In your everyday life, you're always fighting off pathogens. Most of the time you don't even realize it. If you have an underlying condition, it makes it more challenging to fight off a virus like this. You may develop a fever, shortness of breath or a cough more easily than someone who doesn't have a preexisting illness."

Additionally, there are more specific reasons why each condition has its own vulnerabilities. Here's a guide to underlying conditions affected by coronavirus and why, and how you can protect yourself or an at-risk loved one.

Eight out of 10 deaths reported in the U.S. have been in adults ages 65 and older, according to the CDC. Older adults have also been more likely to require hospitalization and admission to an intensive care unit.

Older adults are more likely to have long-term health problems that can increase their risk for infection and serious disease. And, our immune systems usually weaken with age, making it more difficult for people to fight off infections, according to Johns Hopkins Medicine.

The quality of our lung tissue also declines over time, becoming more elastic and making respiratory diseases such as COVID-19 of important concern because of the potential for lung damage.

Inflammation in older adults can be more intense, leading to organ damage.

People with chronic airway and lung diseases such as chronic obstructive pulmonary disease, asthma, pulmonary fibrosis and interstitial lung disease can lay the foundations for more severe infection with coronavirus because of the inflammation, scarring and lung damage those conditions cause, Johns Hopkins Medicine reported.

COVID-19 affects a person's airway and lungs, but those organs work together to provide the body with oxygen. When the lungs are overburdened with an infection, the heart has to work harder, which exacerbates the challenges of people already living with heart disease.

According to the CDC, many conditions can cause a person to be immunocompromised, including cancer treatment, smoking, bone marrow or organ transplantation and immune deficiencies. Poorly controlled HIV or AIDS and prolonged use of man-made steroid hormones or other immune-weakening medications can also hamper a person's immune function.

Cancer can weaken immunity by spreading into the bone marrow, which makes blood cells that help fight infection, according to Cancer Research UK. Cancer prevents bone marrow from making enough blood cells.

Some cancer treatments can temporarily weaken the immune system, too. Because cancer treatments such as chemotherapy, cancer drugs, radiotherapy or steroids are targeted toward cancer cells, they can also diminish the number of white blood cells created in the bone marrow.

A 2017 study found cigarette smoking can harm the immune system by either causing extreme immune responses to pathogens or rendering the body less effective at fighting disease. This may occur by smoking, negatively altering the cellular and molecular mechanisms responsible for keeping an immune system strong.

When a person undergoes a bone marrow transplant using stem cells from a donor, or they receive an organ, a doctor may prescribe medications to prevent graft-versus-host disease and mitigate the immune system's reaction by suppressing its function. After the operation, it takes time for your immune system to be up and running again.

HIV and AIDS attack the body's immune system, specifically the body's T cells, which help the immune system fight off infection. When the diseases are untreated, HIV reduces the number of those cells, making the person more likely to contract other infections or infection-related cancer, according to the CDC.

People with severe obesity, or a body mass index of 40 or higher, are at higher risk of serious disease.

"Obesity shares with most chronic diseases the presence of an inflammatory component," a 2012 study said. Inflammatory responses were linked between the immune system and body fat. Obesity is known to impair immune function by altering white blood cell count as well as the cells that control immune responses.

People with type 1 or type 2 diabetes face an increased risk of getting really sick with COVID-19, as both cause a blood sugar spike. If blood sugar is poorly managed, viral diseases can be more dangerous as high blood sugar may give viruses a place to thrive, according to Diabetes in Control, a news and information resource for medical professionals.

Higher levels of inflammation have been discovered in the bodies of people with diabetes, weakening the immune system and making it more difficult for those affected to stave off sickness in general.

The kidneys produce several hormones that affect immune responses. Having kidney disease and failure can weaken your immune system, making it easier for infections to take hold. According to the National Kidney Foundation, doctors and researchers have found that most infections are worse in people with kidney disease.

The liver is an integral member of the body's line of defense, helping to regulate the number of white blood cells utilized in immune responses and defend against harmful pathogens. Someone with liver disease is experiencing abnormalities in the function of the immune system, giving rise to more serious illness.

Neurological and neurodevelopmental conditions may also increase the risk of serious COVID-19 for people of any age.

These include disorders of the brain, spinal cord, peripheral nerve and muscle such as cerebral palsy, epilepsy, stroke and intellectual disability, according to the CDC. Those with moderate to severe developmental delay, muscular dystrophy or spinal cord injury are also more at-risk.

People with neurological conditions may not be more at risk due to solely their condition, but because medications they might take to control their condition could hamper their immune system. However, some neurological conditions, such as Parkinson's, have been recognized to have inflammatory components, which may harm the immune system.

Others including muscular dystrophy, multiple sclerosis or amyotrophic lateral sclerosis (ALS) could cause paralysis to the diaphragm, which leaves those affected very at risk for respiratory failure if they were to be sick with COVID-19.

If you see yourself on the list of those at higher risk for severe illness, there are several things you can do to protect yourself. First, make sure you are contact your doctor or doctors about your risk level. Second, be extra vigilant about the recommendations that most people are being asked to follow.

Stay home whenever possible and avoid close contact with people, the CDC suggests. Wash your hands often to prevent transferring the virus from a surface to your face, and try to clean and disinfect frequently touched surfaces as often as you can.

If you don't have an underlying condition, doing your part by practicing these cautionary measures can help protect not only you, but your loved ones with existing conditions.

Read more:
What are the underlying conditions causing more serious illness from coronavirus? - WPBF West Palm Beach

News Release

Wednesday, April 15, 2020

NIH-funded study offers new path to modeling eye disease, advancing therapies

Researchers have discovered a technique for directly reprogramming skin cells into light-sensing rod photoreceptors used for vision. The lab-made rods enabled blind mice to detect light after the cells were transplanted into the animals eyes. The work, funded by the National Eye Institute (NEI), published April 15 in Nature. The NEI is part of the National Institutes of Health.

Up until now, researchers have replaced dying photoreceptors in animal models by creating stem cells from skin or blood cells, programming those stem cells to become photoreceptors, which are then transplanted into the back of the eye. In the new study, scientists show that it is possible to skip the stem-cell intermediary step and directly reprogram skins cells into photoreceptors for transplantation into the retina.

This is the first study to show that direct, chemical reprogramming can produce retinal-like cells, which gives us a new and faster strategy for developing therapies for age-related macular degeneration and other retinal disorders caused by the loss of photoreceptors, said Anand Swaroop, Ph.D., senior investigator in the NEI Neurobiology, Neurodegeneration, and Repair Laboratory, which characterized the reprogrammed rod photoreceptor cells by gene expression analysis.

Of immediate benefit will be the ability to quickly develop disease models so we can study mechanisms of disease. The new strategy will also help us design better cell replacement approaches, he said.

Scientists have studied induced pluripotent stem (iPS) cells with intense interest over the past decade. IPSCs are developed in a lab from adult cells rather than fetal tissue and can be used to make nearly any type of replacement cell or tissue. But iPS cell reprogramming protocols can take six months before cells or tissues are ready for transplantation. By contrast, the direct reprogramming described in the current study coaxed skin cells into functional photoreceptors ready for transplantation in only 10 days. The researchers demonstrated their technique in mouse eyes, using both mouse- and human-derived skin cells.

Our technique goes directly from skin cell to photoreceptor without the need for stem cells in between, said the studys lead investigator, Sai Chavala, M.D., CEO and president of CIRC Therapeutics and the Center for Retina Innovation. Chavala is also director of retina services at KE Eye Centers of Texas and a professor of surgery at Texas Christian University and University of North Texas Health Science Center (UNTHSC) School of Medicine, Fort Worth.

Direct reprogramming involves bathing the skin cells in a cocktail of five small molecule compounds that together chemically mediate the molecular pathways relevant for rod photoreceptor cell fate. The result are rod photoreceptors that mimic native rods in appearance and function.

The researchers performed gene expression profiling, which showed that the genes expressed by the new cells were similar to those expressed by real rod photoreceptors. At the same time, genes relevant to skin cell function had been downregulated.

The researchers transplanted the cells into mice with retinal degeneration and then tested their pupillary reflexes, which is a measure of photoreceptor function after transplantation. Under low-light conditions, constriction of the pupil is dependent on rod photoreceptor function. Within a month of transplantation, six of 14 (43%) animals showed robust pupil constriction under low light compared to none of the untreated controls.

Moreover, treated mice with pupil constriction were significantly more likely to seek out and spend time in dark spaces compared with treated mice with no pupil response and untreated controls. Preference for dark spaces is a behavior that requires vision and reflects the mouses natural tendency to seek out safe, dark locations as opposed to light ones.

Even mice with severely advanced retinal degeneration, with little chance of having living photoreceptors remaining, responded to transplantation. Such findings suggest that the observed improvements were due to the lab-made photoreceptors rather than to an ancillary effect that supported the health of the hosts existing photoreceptors, said the studys first author Biraj Mahato, Ph.D., research scientist, UNTHSC.

Three months after transplantation, immunofluorescence studies confirmed the survival of the lab-made photoreceptors, as well as their synaptic connections to neurons in the inner retina.

Further research is needed to optimize the protocol to increase the number of functional transplanted photoreceptors.

Importantly, the researchers worked out how this direct reprogramming is mediated at the cellular level. These insights will help researchers apply the technique not only to the retina, but to many other cell types, Swaroop said.

If efficiency of this direct conversion can be improved, this may significantly reduce the time it takes to develop a potential cell therapy product or disease model, said Kapil Bharti, Ph.D., senior investigator and head of the Ocular and Stem Cell Translational Research Section at NEI.

Chavala and his colleagues are planning a clinical trial to test the therapy in humans for degenerative retinal diseases, such as retinitis pigmentosa.

The work was supported by grants EY021171, EY025667, EY025905, and EY025717 and NEI Intramural Research Program grants ZIAEY000450, ZIAEY000474 and ZIAEY000546.

The University of North Texas has a patent pending on the chemical reprogramming method reported in this paper. CIRC Therapeutics is a start-up company that plans to commercialize treatments using the technology.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

NEI leads the federal governments research on the visual system and eye diseases. NEI supports basic and clinical science programs to develop sight-saving treatments and address special needs of people with vision loss. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

Mahato B, Kaya KD , Fan Y, Sumien N, Shetty RA, Zhang W, Davis D, Mock T , Batabyal S, Ni A, Mohanty S, Han Z, Farjo R, Forster M, Swaroop A and Chavala SH. Pharmacologic fibroblast reprogramming into photoreceptors restores vision. Published online April 15, 2020 in Nature.http://dx.doi.org/10.1038/s41586-020-2201-4

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Researchers restore sight in mice by turning skin cells into light-sensing eye cells - National Institutes of Health

Supplemental Biologics License Application (sBLA) Accepted for KEYTRUDA Monotherapy in Patients Whose Tumors Are Tumor Mutational Burden-High (TMB-H) Who Have Progressed Following Prior Treatment

Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has accepted and granted priority review for a new supplemental Biologics License Application (sBLA) for KEYTRUDA, Merck's anti-PD-1 therapy. The application seeks accelerated approval of KEYTRUDA monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high (TMB-H) 10 mutations/megabase, as determined by an FDA-approved test, who have progressed following prior treatment and who have no satisfactory alternative treatment options. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 16, 2020.

"From the start, biomarker research has been a critical aspect of our clinical program evaluating KEYTRUDA monotherapy," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. "TMB has been an area of scientific interest to help identify patients most likely to benefit from KEYTRUDA. We look forward to working with the FDA throughout the review process to help bring KEYTRUDA monotherapy to patients with cancer in the second-line or higher treatment setting, where options remain limited."

The application was based in part on results from the Phase 2 KEYNOTE-158 trial, which also supported Merck's 2017 FDA approval for KEYTRUDA as the first cancer treatment based on a biomarker, regardless of cancer type, in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. MSI-H is on the highest end of the TMB spectrum. Data from KEYNOTE-158 on the TMB-H patient population were presented at the European Society for Medical Oncology (ESMO) 2019 Congress.

About KEYNOTE-158

KEYNOTE-158 (NCT02628067) is a multicenter, multi-cohort, non-randomized, open-label trial evaluating KEYTRUDA (200 mg every three weeks) in patients with solid tumors. Tissue TMB status was determined using the Foundation Medicine, Inc. FoundationOneCDx assay. Tumor response was assessed every nine weeks per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by independent, central, blinded radiographic review. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by blinded independent central review (BICR) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

About KEYTRUDA (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,200 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA (pembrolizumab) Indications

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Non-Small Cell Lung Cancer

KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, is indicated for the first-line treatment of patients with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with NSCLC expressing PD-L1 [tumor proportion score (TPS) 1%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and is stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA.

Small Cell Lung Cancer

KEYTRUDA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least 1 other prior line of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Head and Neck Squamous Cell Cancer

KEYTRUDA, in combination with platinum and fluorouracil (FU), is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [combined positive score (CPS) 1] as determined by an FDA-approved test.

KEYTRUDA, as a single agent, is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after 3 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Primary Mediastinal Large B-Cell Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. KEYTRUDA is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score (CPS) 10], as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

KEYTRUDA is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

KEYTRUDA is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Esophageal Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus whose tumors express PD-L1 (CPS 10) as determined by an FDA-approved test, with disease progression after one or more prior lines of systemic therapy.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy whose tumors express PD-L1 (CPS 1) as determined by an FDA-approved test. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma (MCC). This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of patients with advanced renal cell carcinoma (RCC).

Selected Important Safety Information for KEYTRUDA

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Pneumonitis occurred in 3.4% (94/2799) of patients with various cancers receiving KEYTRUDA, including Grade 1 (0.8%), 2 (1.3%), 3 (0.9%), 4 (0.3%), and 5 (0.1%). Pneumonitis occurred in 8.2% (65/790) of NSCLC patients receiving KEYTRUDA as a single agent, including Grades 3-4 in 3.2% of patients, and occurred more frequently in patients with a history of prior thoracic radiation (17%) compared to those without (7.7%). Pneumonitis occurred in 6% (18/300) of HNSCC patients receiving KEYTRUDA as a single agent, including Grades 3-5 in 1.6% of patients, and occurred in 5.4% (15/276) of patients receiving KEYTRUDA in combination with platinum and FU as first-line therapy for advanced disease, including Grades 3-5 in 1.5% of patients.

Monitor patients for signs and symptoms of pneumonitis. Evaluate suspected pneumonitis with radiographic imaging. Administer corticosteroids for Grade 2 or greater pneumonitis. Withhold KEYTRUDA for Grade 2; permanently discontinue KEYTRUDA for Grade 3 or 4 or recurrent Grade 2 pneumonitis.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis. Colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 2 (0.4%), 3 (1.1%), and 4 (<0.1%). Monitor patients for signs and symptoms of colitis. Administer corticosteroids for Grade 2 or greater colitis. Withhold KEYTRUDA for Grade 2 or 3; permanently discontinue KEYTRUDA for Grade 4 colitis.

Immune-Mediated Hepatitis (KEYTRUDA) and Hepatotoxicity (KEYTRUDA in Combination With Axitinib)

Immune-Mediated Hepatitis

KEYTRUDA can cause immune-mediated hepatitis. Hepatitis occurred in 0.7% (19/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.4%), and 4 (<0.1%). Monitor patients for changes in liver function. Administer corticosteroids for Grade 2 or greater hepatitis and, based on severity of liver enzyme elevations, withhold or discontinue KEYTRUDA.

Hepatotoxicity in Combination With Axitinib

KEYTRUDA in combination with axitinib can cause hepatic toxicity with higher than expected frequencies of Grades 3 and 4 ALT and AST elevations compared to KEYTRUDA alone. With the combination of KEYTRUDA and axitinib, Grades 3 and 4 increased ALT (20%) and increased AST (13%) were seen. Monitor liver enzymes before initiation of and periodically throughout treatment. Consider more frequent monitoring of liver enzymes as compared to when the drugs are administered as single agents. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and consider administering corticosteroids as needed.

Immune-Mediated Endocrinopathies

KEYTRUDA can cause adrenal insufficiency (primary and secondary), hypophysitis, thyroid disorders, and type 1 diabetes mellitus. Adrenal insufficiency occurred in 0.8% (22/2799) of patients, including Grade 2 (0.3%), 3 (0.3%), and 4 (<0.1%). Hypophysitis occurred in 0.6% (17/2799) of patients, including Grade 2 (0.2%), 3 (0.3%), and 4 (<0.1%). Hypothyroidism occurred in 8.5% (237/2799) of patients, including Grade 2 (6.2%) and 3 (0.1%). The incidence of new or worsening hypothyroidism was higher in 1185 patients with HNSCC (16%) receiving KEYTRUDA, as a single agent or in combination with platinum and FU, including Grade 3 (0.3%) hypothyroidism. Hyperthyroidism occurred in 3.4% (96/2799) of patients, including Grade 2 (0.8%) and 3 (0.1%), and thyroiditis occurred in 0.6% (16/2799) of patients, including Grade 2 (0.3%). Type 1 diabetes mellitus, including diabetic ketoacidosis, occurred in 0.2% (6/2799) of patients.

Monitor patients for signs and symptoms of adrenal insufficiency, hypophysitis (including hypopituitarism), thyroid function (prior to and periodically during treatment), and hyperglycemia. For adrenal insufficiency or hypophysitis, administer corticosteroids and hormone replacement as clinically indicated. Withhold KEYTRUDA for Grade 2 adrenal insufficiency or hypophysitis and withhold or discontinue KEYTRUDA for Grade 3 or Grade 4 adrenal insufficiency or hypophysitis. Administer hormone replacement for hypothyroidism and manage hyperthyroidism with thionamides and beta-blockers as appropriate. Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism. Administer insulin for type 1 diabetes, and withhold KEYTRUDA and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-Mediated Nephritis and Renal Dysfunction

KEYTRUDA can cause immune-mediated nephritis. Nephritis occurred in 0.3% (9/2799) of patients receiving KEYTRUDA, including Grade 2 (0.1%), 3 (0.1%), and 4 (<0.1%) nephritis. Nephritis occurred in 1.7% (7/405) of patients receiving KEYTRUDA in combination with pemetrexed and platinum chemotherapy. Monitor patients for changes in renal function. Administer corticosteroids for Grade 2 or greater nephritis. Withhold KEYTRUDA for Grade 2; permanently discontinue for Grade 3 or 4 nephritis.

Immune-Mediated Skin Reactions

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur. Monitor patients for suspected severe skin reactions and based on the severity of the adverse reaction, withhold or permanently discontinue KEYTRUDA and administer corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA and refer the patient for specialized care for assessment and treatment. If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Other Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue in patients receiving KEYTRUDA and may also occur after discontinuation of treatment. For suspected immune-mediated adverse reactions, ensure adequate evaluation to confirm etiology or exclude other causes. Based on the severity of the adverse reaction, withhold KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Resume KEYTRUDA when the adverse reaction remains at Grade 1 or less following corticosteroid taper. Permanently discontinue KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions occurred in less than 1% (unless otherwise indicated) of 2799 patients: arthritis (1.5%), uveitis, myositis, Guillain-Barr syndrome, myasthenia gravis, vasculitis, pancreatitis, hemolytic anemia, sarcoidosis, and encephalitis. In addition, myelitis and myocarditis were reported in other clinical trials, including classical Hodgkin lymphoma, and postmarketing use.

Treatment with KEYTRUDA may increase the risk of rejection in solid organ transplant recipients. Consider the benefit of treatment vs the risk of possible organ rejection in these patients.

Infusion-Related Reactions

KEYTRUDA can cause severe or life-threatening infusion-related reactions, including hypersensitivity and anaphylaxis, which have been reported in 0.2% (6/2799) of patients. Monitor patients for signs and symptoms of infusion-related reactions. For Grade 3 or 4 reactions, stop infusion and permanently discontinue KEYTRUDA.

Complications of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Immune-mediated complications, including fatal events, occurred in patients who underwent allogeneic HSCT after treatment with KEYTRUDA. Of 23 patients with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 (26%) developed graft-versus-host disease (GVHD) (1 fatal case) and 2 (9%) developed severe hepatic veno-occlusive disease (VOD) after reduced-intensity conditioning (1 fatal case). Cases of fatal hyperacute GVHD after allogeneic HSCT have also been reported in patients with lymphoma who received a PD-1 receptorblocking antibody before transplantation. Follow patients closely for early evidence of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), Grade 3 to 4 acute GVHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease (VOD), and other immune-mediated adverse reactions.

In patients with a history of allogeneic HSCT, acute GVHD (including fatal GVHD) has been reported after treatment with KEYTRUDA. Patients who experienced GVHD after their transplant procedure may be at increased risk for GVHD after KEYTRUDA. Consider the benefit of KEYTRUDA vs the risk of GVHD in these patients.

Increased Mortality in Patients With Multiple Myeloma

In trials in patients with multiple myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of these patients with a PD-1 or PD-L1 blocking antibody in this combination is not recommended outside of controlled trials.

Embryofetal Toxicity

Based on its mechanism of action, KEYTRUDA can cause fetal harm when administered to a pregnant woman. Advise women of this potential risk. In females of reproductive potential, verify pregnancy status prior to initiating KEYTRUDA and advise them to use effective contraception during treatment and for 4 months after the last dose.

Adverse Reactions

In KEYNOTE-006, KEYTRUDA was discontinued due to adverse reactions in 9% of 555 patients with advanced melanoma; adverse reactions leading to permanent discontinuation in more than one patient were colitis (1.4%), autoimmune hepatitis (0.7%), allergic reaction (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The most common adverse reactions (20%) with KEYTRUDA were fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-002, KEYTRUDA was permanently discontinued due to adverse reactions in 12% of 357 patients with advanced melanoma; the most common (1%) were general physical health deterioration (1%), asthenia (1%), dyspnea (1%), pneumonitis (1%), and generalized edema (1%). The most common adverse reactions were fatigue (43%), pruritus (28%), rash (24%), constipation (22%), nausea (22%), diarrhea (20%), and decreased appetite (20%).

In KEYNOTE-054, KEYTRUDA was permanently discontinued due to adverse reactions in 14% of 509 patients; the most common (1%) were pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Serious adverse reactions occurred in 25% of patients receiving KEYTRUDA. The most common adverse reaction (20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 20% of 405 patients. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonitis (3%) and acute kidney injury (2%). The most common adverse reactions (20%) with KEYTRUDA were nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased appetite (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and either paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued due to adverse reactions in 15% of 101 patients. The most frequent serious adverse reactions reported in at least 2% of patients were febrile neutropenia, pneumonia, and urinary tract infection. Adverse reactions observed in KEYNOTE-407 were similar to those observed in KEYNOTE-189 with the exception that increased incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) were observed in the KEYTRUDA and chemotherapy arm compared to the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued due to adverse reactions in 19% of 636 patients with advanced NSCLC; the most common were pneumonitis (3%), death due to unknown cause (1.6%), and pneumonia (1.4%). The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The most common adverse reaction (20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued due to adverse reactions in 8% of 682 patients with metastatic NSCLC; the most common was pneumonitis (1.8%). The most common adverse reactions (20%) were decreased appetite (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

Adverse reactions occurring in patients with SCLC were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent.

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued due to adverse events in 12% of 300 patients with HNSCC; the most common adverse reactions leading to permanent discontinuation were sepsis (1.7%) and pneumonia (1.3%). The most common adverse reactions (20%) were fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered in combination with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued due to adverse reactions in 16% of 276 patients with HNSCC. The most common adverse reactions resulting in permanent discontinuation of KEYTRUDA were pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The most common adverse reactions (20%) were nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal inflammation (31%), diarrhea (29%), decreased appetite (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued due to adverse reactions in 17% of 192 patients with HNSCC. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions reported in at least 2% of patients were pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The most common adverse reactions (20%) were fatigue, decreased appetite, and dyspnea. Adverse reactions occurring in patients with HNSCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-087, KEYTRUDA was discontinued due to adverse reactions in 5% of 210 patients with cHL. Serious adverse reactions occurred in 16% of patients; those 1% included pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two patients died from causes other than disease progression; 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The most common adverse reactions (20%) were fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal pain (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued due to adverse reactions in 8% of 53 patients with PMBCL. Serious adverse reactions occurred in 26% of patients and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) patients died within 30 days of start of treatment. The most common adverse reactions (20%) were musculoskeletal pain (30%), upper respiratory tract infection and pyrexia (28% each), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued due to adverse reactions in 11% of 370 patients with locally advanced or metastatic urothelial carcinoma. Serious adverse reactions occurred in 42% of patients; those 2% were urinary tract infection, hematuria, acute kidney injury, pneumonia, and urosepsis. The most common adverse reactions (20%) were fatigue (38%), musculoskeletal pain (24%), decreased appetite (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued due to adverse reactions in 8% of 266 patients with locally advanced or metastatic urothelial carcinoma. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.9%). Serious adverse reactions occurred in 39% of KEYTRUDA-treated patients; those 2% were urinary tract infection, pneumonia, anemia, and pneumonitis. The most common adverse reactions (20%) in patients who received KEYTRUDA were fatigue (38%), musculoskeletal pain (32%), pruritus (23%), decreased appetite (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued due to adverse reactions in 11% of 148 patients with high-risk NMIBC. The most common adverse reaction resulting in permanent discontinuation of KEYTRUDA was pneumonitis (1.4%). Serious adverse reactions occurred in 28% of patients; those 2% were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (20%) were fatigue (29%), diarrhea (24%), and rash (24%).

Adverse reactions occurring in patients with gastric cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

Adverse reactions occurring in patients with esophageal cancer were similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued due to adverse reactions in 8% of 98 patients with recurrent or metastatic cervical cancer. Serious adverse reactions occurred in 39% of patients receiving KEYTRUDA; the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% each). The most common adverse reactions (20%) were fatigue (43%), musculoskeletal pain (27%), diarrhea (23%), pain and abdominal pain (22% each), and decreased appetite (21%).

Adverse reactions occurring in patients with hepatocellular carcinoma (HCC) were generally similar to those in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy, with the exception of increased incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the 50 patients with MCC enrolled in study KEYNOTE-017, adverse reactions occurring in patients with MCC were generally similar to those occurring in patients with melanoma or NSCLC who received KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence were elevated AST (11%) and hyperglycemia (19%).

More:
Merck Receives Priority Review from FDA for Second Application for KEYTRUDA (pembrolizumab) Based on Biomarker, Regardless of Tumor Type - Benzinga

Newswise (New York, NY April 9, 2020) Mount Sinai Health System is the first in the country to use an innovative allogeneic stem cell therapy in COVID-19 patients and will play a central role in developing and conducting a rigorous clinical trial for patients with severe acute respiratory distress syndrome, the breathing illness that afflicts people who have severe cases of COVID-19.

The therapy, known as remestemcel-L, has previously been tested in bone marrow transplant patients, who can experience an overactive immune response similar to that seen in severe cases of COVID-19.

Mount Sinai began administering the therapy, known as remestemcel-L, to patients in late March under the Food and Drug Administrations compassionate use program, which allows patients with an immediately life-threatening condition to gain access to an investigational therapy. Ten patients with moderate to severe cases of COVID-19-related acute respiratory distress syndrome (ARDS), most of whom were on ventilators, were given the therapy and doctors saw encouraging results.

We are encouraged by what we have seen so far and look forward to participating in the randomized controlled trial starting soon that would better indicate whether this is an effective therapy for patients in severe respiratory distress from COVID-19, said Keren Osman, MD, Medical Director of the Cellular Therapy Service in the Bone Marrow and Stem Cell Transplantation Program at The Tisch Cancer Institute at Mount Sinai and Associate Professor of Medicine (Hematology and Medical Oncology) at the Icahn School of Medicine at Mount Sinai. Dr. Osman oversaw the treatment of the first Mount Sinai patients with this innovative therapy.

Under the leadership of Annetine Gelijns, PhD, Alan Moskowitz, MD, and Emilia Bagiella, PhD, of Mount Sinais Institute of Transformative Clinical Trials, Mount Sinai will serve as the clinical and data coordinating center for a randomized clinical trial evaluating the therapeutic benefit and safety of this stem cell therapy in 240 patients with COVID-related ARDS in the United States and Canada. The trial will be conducted as a public-private partnership between the Cardiothoracic Surgical Trials Network, which was established as a flexible clinical trials platform by the National Heart, Lung, and Blood Institute, and Mesoblast, the manufacturer of the cells.

The coronavirus pandemic has caused exponential increases of people suffering with acute respiratory distress syndrome, requiring intubation and mechanical ventilation with many dying, said Dr. Gelijns, who is also the Edmond A. Guggenheim Professor of Health Policy at the Icahn School of Medicine at Mount Sinai. We have designed a clinical trial that will expeditiously determine whether the stem cell therapy will offer a life-saving therapy for a group of patients with a dismal prognosis.

We are interested to study the potential of this anti-inflammatory cell therapy to make an impact on the high mortality of lung complications in COVID-19 patients, said CSTN Chairman A. Marc Gillinov, MD. This randomized controlled trial is in line with our mandate to rigorously evaluate novel therapies for public health imperatives.

The therapy consists of mesenchymal stem cells. These cells are found in bone marrow and serve many functions including aiding tissue repair and suppressing inflammation. The therapy was previously tested in a phase 3 trial in children who had an often-fatal inflammatory condition called graft-versus-host disease (GVHD) that can occur after bone marrow transplants.

The inflammation that occurs in GVHD is the result of a cytokine storm, which activates immune cells that attack healthy tissue. A similar cytokine storm that causes damage to the lungs and other organs appears to be taking place in COVID-19 patients who develop acute respiratory distress syndrome, said John Levine, MD, Professor of Medicine (Hematology and Medical Oncology), and Pediatrics, at the Icahn School of Medicine at Mount Sinai, who helped implement the compassionate use of the drug at Mount Sinai.

These stem cells have shown excellent response rates in severe graft-versus-host disease in children, said Dr. Levine, who is also the co-director of the Mount Sinai Acute GVHD International Consortium (MAGIC). Mesenchymal stem cells have a natural property that dampens excessive immune responses.

Several people were instrumental in quickly and efficiently working through the complex application process for each patient to gain compassionate use of the therapy. Three key players involved were Stacey-Ann Brown, MD, MPH, Assistant Professor of Medicine (Pulmonary, Critical Care and Sleep Medicine) at the Icahn School of Medicine at Mount Sinai; Tiffany Drummond, Assistant Director of Regulatory Affairs at The Tisch Cancer Institute at Mount Sinai; and Camelia Iancu-Rubin, PhD, Director of the Cellular Therapy Laboratory at the Icahn School of Medicine at Mount Sinai.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality carefrom prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 onU.S. News & World Report's"Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally byU.S. News & World Report.

For more information, visithttps://www.mountsinai.orgor find Mount Sinai onFacebook,TwitterandYouTube.

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Mount Sinai Leading the Way in Innovative Stem Cell Therapy for COVID-19 Patients - Newswise

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Global 3D Bioprinting market was highly consolidated with key players accounting for significant share in 2018. Prominent players operating in the Global 3D Bioprinting Market are: Solidscape, Inc. (acquired by Prodways Group), TeVido BioDevices, LLC, 3Dynamics Systems Ltd., Bio3D Technologies Pte. Ltd., Aspect Biosystems Ltd., Stratasys Ltd., Luxexcel Group B.V., Materialise N.V., Cyfuse Biomedical K.K., Voxeljet A.G., Envision TEC, and Organovo Holding, Inc., among others.

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Global 3D Bioprinting Market is anticipated to reach at market value of US$ 1.4 Bn by 2027 - Galus Australis