Category Archives: Gene Medicine

Friday, May 1, 2020

At least 2 billion people around the world have vision problems but how do you know if and when your pet is struggling with its own eyesight? Its a good question, especially in a year numbered 2020.

Dr. Wendy Townsend, associate professor of ophthalmology in Purdue Veterinary Medicines Department of Veterinary Clinical Sciences, has focused her career and research in veterinary medicine on diagnosing and treating eye conditions in animals. The most common question I get is if we fit animals with glasses, Dr. Townsend says. While thats not what we do, our goal is to help animals see better and improve their quality of life if theyre having issues.

Although her patients span a variety of species, her research is focused on a particular breed of dog that reigns as one of the most popular dog breeds in America: golden retrievers. Golden retriever pigmentary uveitis is a disease almost exclusively found in purebred golden retrievers. Its an inherited form of uveitis (inflammation of the uveal tract, which includes the iris). And though the disease is inherited, the onset and diagnosis usually occurs when the dogs are older.

The disease can often result in blindness due to cataracts and glaucoma, and there are no current methods to prevent or reverse it. Mild symptoms, such as redness and drainage, usually dont appear until the dog is around eight years old and can progress to an advanced stage before dogs see a veterinarian, Dr. Townsend says. The disease affects about 10% of senior golden retrievers.

Dr. Townsend is leading a study that is trying to identify the gene that causes the disease. If the gene can be identified, the disease can be detected earlier, and breeders will be able to identify which of their dogs might be carriers and how they can keep the disease from being passed on to future generations.

The problem breeders are facing right now is that even if theyre being responsible and making good decisions, they dont know their dog is affected, Dr. Townsend says. They can be several generations down their pedigree before they know theres a problem.

Dr. Townsend grew up owning golden retrievers and was completing her residency in veterinary ophthalmology when the disease was first recognized. It was bizarre because nobody could understand why it was happening in this specific breed, Dr. Townsend says. But since I loved golden retrievers and had a passion for ophthalmology, it seemed like a natural fit.

And although the disease presents itself primarily in purebred golden retrievers, Dr. Townsend explains that it can appear in some crossbreeds especially Labrador and golden retriever crosses. That becomes a concern because Labrador and golden crosses are frequently used as seeing-eye dogs, Dr. Townsend says. And because the disease doesnt show symptoms until these dogs are older, they could be struggling with their own vision and you might not even know.

Thats why Dr. Townsend says having dogs screened especially service dogs is critical. The earlier you can catch something, the better, Dr. Townsend says. That goes for all vision problems with any animal.

As a veterinary ophthalmologist, Dr. Townsend says its not uncommon for her to see dogs from across the country affected by golden retriever pigmentary uveitis. In addition to those patients, she commonly sees animals with corneal ulcers (scratches on the eye), cataracts, and glaucoma. Her patients include mostly dogs, horses, and cats but she also has treated penguins, tigers, and other exotic species.

And although she doesnt fit animals with glasses, she has fitted a dog or two with contact lenses. Theyre usually dogs that participate in agility and have trouble focusing or struggle with nearsightedness.

Sometimes animals struggle with the same eye problems that people do. Theyre just not as good at telling us when something is wrong, Dr. Townsend says. She consistently encourages pet owners to be cognizant of their pets eye health for that very reason.

Animals are good at compensating when something isnt working right. So if one eye is bothering them, theyll just rely more heavily on the other eye, Dr. Townsend says. And most of our pets dont need to have super-sharp vision to lead normal everyday lives. But in some cases like with dogs that participate in agility being able to focus both near and far is important.

As Dr. Townsend continues her mission to solve the mystery behind golden retriever pigmentary uveitis in addition to seeing her patients she hopes she can build some awareness around the field of ophthalmology. The eye might be small, but its a powerful organ that we all use and it allows me to work across a wide variety of species, Dr. Townsend explains. I frequently have clients tell me, I had no idea this was an option, or, I didnt know there were eye doctors for dogs. The impact this field can have on our patients and their quality of life can be significant.

Dr. Townsends work is supported by the American Kennel Clubs Canine Health Foundation.

Writer(s): Abbey Nickel, Purdue News Service, and Kevin Doerr | pvmnews@purdue.edu

Read more from the original source:
More Than Meets the Eye: Veterinary Ophthalmologist Wendy Townsend Focuses on Animal Eye Conditions - Purdue Veterinary News

April 28, 2020

Rochester research into RNA structure and function provides key information for developing coronavirus treatments.

Viruses like the coronavirus that causes COVID-19 are able to unleash their fury because of a devious weapon: ribonucleic acid, also known as RNA.

A contingent of researchers at the University of Rochester study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. As COVID-19 continues to spread around the globe, RNA research provides an important foundation for developing antiviral drugs, vaccines, and other therapeutics to disrupt the virus and stop infections.

The Universitys website is a way to find guidance and critical information during a rapidly changing situation.

Find out what to do if you or a close contact have symptoms or think you may have been exposed.

Understanding RNA structure and function helps us understand how to throw a therapeutic wrench into what the COVID-19 RNA doesmake new virus that can infect more of our cells and also the cells of other human beings, says Lynne Maquat, professor of biochemistry and biophysics at the University of Rochester Medical Center and the director of Rochesters Center for RNA Biology.

In the past few decades, as scientists came to realize that genetic material is largely regulated by the RNA it encodes, that most of our DNA produces RNA, and that RNA is not only a target but also a tool for disease therapies, the RNA research world has exploded, Maquat says. The University of Rochester understood this.

In 2007, Maquat founded the Center for RNA Biology as a means of conducting interdisciplinary research in the function, structure, and processing of RNAs. The center involves researchers from both the River Campus and the Medical Center, combining expertise in biology, chemistry, engineering, neurology, and pharmacology.

While much of the research across the University has been put on pause, labs that are involved in coronavirus research remain active.

Our strength as a university is our diversity of research expertise, combined with our highly collaborative nature, says Dragony Fu, an assistant professor of biology on the River Campus and a member of the Center for RNA Biology. We are surrounded by outstanding researchers who enhance our understanding of RNA biology, and a medical center that provides a translational aspect where the knowledge gained from RNA biology can be applied for therapeutics.

In mammals, such as humans, DNA contains genetic instructions that are transcribedor copiedinto RNA. While DNA remains in the cells nucleus, RNA carries the copies of genetic information to the rest of the cell by way of various combinations of amino acids, which it delivers to ribosomes. The ribosomes link the amino acids together to form proteins that then carry out functions within the human body.

Many diseases occur when these gene expressions go awry.

COVID-19, short for coronavirus disease 2019, is caused by the novel coronavirus SARS-CoV-2. Like many other viruses, SARS-CoV-2 is an RNA virus. This means that, unlike in humans and other mammals, the genetic material for SARS-CoV-2 is encoded in RNA. The viral RNA is sneaky: its features cause the protein synthesis machinery of our cells to mistake it for RNA produced by our own DNA.

While SARS-CoV-2 is a new coronavirus, it likely replicates and functions similar to related coronaviruses that infect animals and humans, says Douglas Anderson, an assistant professor of medicine in the Aab Cardiovascular Research Institute and a member of the Center for RNA Biology, who studies how RNA mutations can give rise to human disease.

A graphic created by the New York Times illustrates how the coronavirus that causes COVID-19 enters the body through the nose, mouth, or eyes and attaches to our cells. Once the virus is inside our cells, it releases its RNA. Our hijacked cells serve as virus factories, reading the viruss RNA and making long viral proteins to compromise the immune system. The virus assembles new copies of itself and spreads to more parts of the body andby way of saliva, sweat, and other bodily fluidsto other humans.

Once the virus is in our cells, the entire process of infection and re-infection depends on the viral RNA, Maquat says.

Researchers Douglas Anderson, Dragony Fu, and Lynne Maquat are among the scientists at the University of Rochester who study the RNA of viruses to better understand how RNAs work and how they are involved in diseases. (University of Rochester photos / Matt Wittmeyer / J. Adam Fenster)

Maquat has been studying RNA since 1972 and was part of the earliest wave of scientists to realize the important role RNA plays in human health and disease.

Our cells have a number of ways to combat viruses in what can be viewed as an arms race between host and virus. One of the weapons in our cells arsenal is an RNA surveillance mechanism Maquat discovered called nonsense-mediated mRNA decay (NMD).

Nonsense-mediated mRNA decay protects us from many genetic mutations that could cause disease if NMD was not active to destroy the RNA harboring the mutation, she says.

Maquats discovery has contributed to the development of drug therapies for genetic disorders such as cystic fibrosis, and may be useful in developing treatments for coronavirus.

NMD also helps us combat viral infections, which is why many viruses either inhibit or evade NMD, she adds. The genome of the virus COVID-19 is a positive-sense, single-stranded RNA. It is well known that other positive-sense, single-stranded RNA viruses evade NMD by having RNA structures that prevent NMD from degrading viral RNAs.

Maquats lab is currently collaborating with a lab at Harvard University to test how viral proteins can inhibit the NMD machinery.

Like Maquat, Fu studies fundamental aspects of RNAand has found that his research on proteins may, too, be applicable to coronavirus research.

Fus lab analyzes enzymes and proteins that modify the chemical structure of RNA and how these chemical modifications impact the function of RNA. A research group at the University of California, San Francisco, recently identified an interaction between a protein made by the SARS-CoV-9 virus and a protein Fu studies.

This is an intriguing result, and we are currently thinking of ways this interaction could affect the host cell, Fu says. There is emerging evidence that RNA-based viruses undergo RNA modification, so we could use this knowledge to identify key links between the host and pathogen for development of a coronavirus vaccine or treatment.

One of the reasons viruses are such a challenge is that they change and mutate in response to drugs.

Targeting viral RNA, or the proteins it produces, is key for treating this disease.

That means novel virus treatments and vaccines have to be created each time a new strain of virus presents itself. Armed with innovative research on the fundamentals of RNA, scientists are better able to develop and test therapeutics that directly target the RNAs and processes critical to a viruss life cycle.

The University of Rochester Medical Center, for instance, is currently participating in a clinical trial to evaluate the safety and efficacy of a potential coronavirus treatment called remdesivir, an antiviral drug particularly tailored to attack RNA viruses. The drug inhibits RNA polymerase, an enzyme responsible for copying a DNA sequence into an RNA sequence.

Anderson has found that alternative therapeutics, such as the gene-editing technology CRISPR, may additionally usher in a new approach to how we target and combat infectious diseases, he says.

For the past few years, Andersons lab has developed tools and delivery systems that use the RNA-targeting CRISPR-Cas13 to treat human genetic diseases that affect muscle function. CRISPR-Cas13 is like a molecular pair of scissors that can target specific RNAs for degradation, using small, programmable guide RNAs.

When the health crisis first became apparent in Wuhan, China, researchers in Andersons lab turned their focus toward developing a CRISPR-Cas13 therapeutic aimed at SARS-CoV-2. Applying the knowledge already available about coronavirus RNA replication, they designed single CRISPR guide RNAs capable of targeting every viral RNA that is made within a SARS-CoV-2 infected cell. Using a novel cloning method developed in Andersons lab, multiple CRISPR guide-RNAs could be packaged into a single therapeutic vector (a genetically engineered carrier) to target numerous viral RNA sites simultaneously. The multi-pronged targeting strategy could be used as a therapy to safeguard against virus-induced cell toxicity and prevent escape of viruses which may have undergone mutation.

Infectious viruses and pandemics seemingly come out of nowhere, which has made it hard to rapidly develop and screen traditional small molecule therapeutics or vaccines, Anderson says. There is a clear need to develop alternative targeted therapeutics, such as CRISPR-Cas13, which have the ability to be rapidly reprogrammed to target new emerging pandemics.

While many new treatments for the novel coronavirus are being considered, there is one thing that is certain, Maquat says: Targeting viral RNA, or the proteins it produces, is key for treating this disease.

Tags: Arts and Sciences, Center for RNA Biology, COVID-19, Department of Biochemistry and Biophysics, Department of Biology, Douglas Anderson, Dragony Fu, featured-post, Lynne Maquat, medical center

Category: Featured

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COVID-19: What's RNA research got to do with it? - University of Rochester

TEL AVIV & PARSIPPANY, N.J.--(BUSINESS WIRE)-- Teva Pharmaceuticals USA, Inc., an affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today announced that new data for AJOVY (fremanezumab-vfrm) injection and AUSTEDO (deutetrabenazine) tablets have appeared in an online supplement to Neurology. The data includes 23 abstracts that highlight a diverse set of data evaluating the efficacy and safety of AJOVY and AUSTEDO.

The abstracts were originally planned for presentation at the recently cancelled 2020 American Academy of Neurology (AAN) annual meeting. In addition to the online supplement, the abstracts are also available through the AAN online abstracts website.

We are pleased to have an opportunity to share this important data with the neurology community which build upon our understanding of the efficacy and safety of AJOVY and AUSTEDO across various patient populations, and further demonstrate Tevas commitment to the CNS space, said Denisa Hurtukova, MD, VP, Head of North America Medical Affairs. Teva is committed to ongoing evaluation of these significant therapies to help physicians, healthcare providers and most importantly, patients, make informed decisions about their treatments.

The featured abstracts include new AJOVY and AUSTEDO data, including results from an open-label extension of the FOCUS study, a Phase IIIb study that evaluated the efficacy and safety of quarterly and monthly treatment with AJOVY compared to placebo in adult patients with migraine and documented inadequate response to 2-4 classes of prior preventive treatments. Another analysis using the FDA Adverse Events Reporting System (FAERS) provides patient and healthcare professional insight into the real-world experience with CGRP pathway-targeted therapies. In addition, new data is available from a long-term, open-label extension study which examined the safety of AUSTEDO at higher doses beyond the approved maximum dose to treat chorea associated with Huntingtons disease, as well as the long-term experience with AUSTEDO in both younger and older patients with tardive dyskinesia.

The full list of Teva abstracts in the Neurology supplement includes:

AUSTEDO (deutetrabenazine) Tablets:

De Novo:

Encore:

AJOVY (fremanezumab-vfrm) Injection:

De Novo:

Encore:

About AJOVY (fremanezumab-vfrm) injection

AJOVY is available as a 225 mg/1.5 mL single dose injection in a prefilled syringe with two dosing options 225 mg monthly administered as one subcutaneous injection, or 675 mg every three months (quarterly), which is administered as three subcutaneous injections. AJOVY can be administered in office by a healthcare professional or at home by a patient or caregiver. No starting dose is required to begin treatment. The AJOVY autoinjector has been approved by the FDA and is available in the U.S. In addition to the U.S., the AJOVY autoinjector is currently available in Germany and should soon be available in other select European markets.

U.S. Important Safety Information about AJOVY (fremanezumab-vfrm) injection

Contraindications: AJOVY is contraindicated in patients with serious hypersensitivity to fremanezumab-vfrm or to any of the excipients.

Hypersensitivity Reactions: Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria were reported with AJOVY in clinical trials. Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. If a hypersensitivity reaction occurs, consider discontinuing AJOVY and institute appropriate therapy.

Adverse Reactions: The most common adverse reactions (5% and greater than placebo) were injection site reactions.

Please click here for full U.S. Prescribing Information for AJOVY (fremanezumab-vfrm) injection.

About AUSTEDO (deutetrabenazine)

AUSTEDO is a vesicular monoamine transporter 2 (VMAT2) inhibitor approved by the U.S. Food and Drug Administration for the treatment of tardive dyskinesia in adults and for the treatment of chorea associated with Huntingtons disease. Safety and effectiveness in pediatric patients have not been established.

AUSTEDO Indications and Usage

AUSTEDO is indicated for the treatment of chorea associated with Huntingtons disease and for the treatment of tardive dyskinesia in adults.

Important Safety Information About AUSTEDO

Depression and Suicidality in Patients with Huntingtons Disease: AUSTEDO can increase the risk of depression and suicidal thoughts and behavior (suicidality) in patients with Huntingtons disease. Balance the risks of depression and suicidality with the clinical need for treatment of chorea. Closely monitor patients for the emergence or worsening of depression, suicidality, or unusual changes in behavior. Inform patients, their caregivers, and families of the risk of depression and suicidality and instruct them to report behaviors of concern promptly to the treating physician. Exercise caution when treating patients with a history of depression or prior suicide attempts or ideation. AUSTEDO is contraindicated in patients who are suicidal, and in patients with untreated or inadequately treated depression.

Contraindications: AUSTEDO is contraindicated in patients with Huntingtons disease who are suicidal, or have untreated or inadequately treated depression. AUSTEDO is also contraindicated in: patients with hepatic impairment; patients taking reserpine or within 20 days of discontinuing reserpine; patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of discontinuing MAOI therapy; and patients taking tetrabenazine (Xenazine) or valbenazine (Ingrezza).

Clinical Worsening and Adverse Events in Patients with Huntingtons Disease: AUSTEDO may cause a worsening in mood, cognition, rigidity, and functional capacity. Prescribers should periodically re-evaluate the need for AUSTEDO in their patients by assessing the effect on chorea and possible adverse effects.

QTc Prolongation: Tetrabenazine, a closely related VMAT2 inhibitor, causes an increase in the corrected QT (QTc) interval. A clinically relevant QT prolongation may occur in some patients treated with AUSTEDO who are CYP2D6 poor metabolizers or are co-administered a strong CYP2D6 inhibitor. Dose reduction may be necessary. The use of AUSTEDO in combination with other drugs known to prolong QTc may result in clinically significant QT prolongations. For patients requiring AUSTEDO doses greater than 24 mg per day who are using AUSTEDO with other drugs known to prolong QTc, assess the QTc interval before and after increasing the dose of AUSTEDO or the other drugs. AUSTEDO should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported in association with drugs that reduce dopaminergic transmission, has been observed in patients receiving tetrabenazine. The risk may be increased by concomitant use of dopamine antagonists or antipsychotics. The management of NMS should include immediate discontinuation of AUSTEDO; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems.

Akathisia, Agitation, and Restlessness: AUSTEDO may increase the risk of akathisia, agitation, and restlessness. The risk of akathisia may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops akathisia, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Parkinsonism: AUSTEDO may cause parkinsonism in patients with Huntingtons disease or tardive dyskinesia. Parkinsonism has also been observed with other VMAT2 inhibitors. The risk of parkinsonism may be increased by concomitant use of dopamine antagonists or antipsychotics. If a patient develops parkinsonism, the AUSTEDO dose should be reduced; some patients may require discontinuation of therapy.

Sedation and Somnolence: Sedation is a common dose-limiting adverse reaction of AUSTEDO. Patients should not perform activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are on a maintenance dose of AUSTEDO and know how the drug affects them. Concomitant use of alcohol or other sedating drugs may have additive effects and worsen sedation and somnolence.

Hyperprolactinemia: Tetrabenazine elevates serum prolactin concentrations in humans. If there is a clinical suspicion of symptomatic hyperprolactinemia, appropriate laboratory testing should be done and consideration should be given to discontinuation of AUSTEDO.

Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to melanin-containing tissues and could accumulate in these tissues over time. Prescribers should be aware of the possibility of long-term ophthalmologic effects.

CYP2D6 Metabolism: In patients who are poor CYP2D6 metabolizers or are taking strong CYP2D6 inhibitors, the total daily dosage of AUSTEDO should not exceed 36 mg (maximum single dose of 18 mg).

Common Adverse Reactions: The most common adverse reactions for AUSTEDO (>8% and greater than placebo) in a controlled clinical study in patients with Huntingtons disease were somnolence, diarrhea, dry mouth, and fatigue. The most common adverse reactions for AUSTEDO (4% and greater than placebo) in controlled clinical studies in patients with tardive dyskinesia were nasopharyngitis and insomnia.

Please see accompanying full Prescribing Information, including Boxed Warning.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve peoples lives for more than a century. We are a global leader in generic and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day, and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com.

Cautionary Note Regarding Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 regarding AJOVY and AUSTEDO, which are based on managements current beliefs and expectations and are subject to substantial risks and uncertainties, both known and unknown, that could cause our future results, performance or achievements to differ significantly from that expressed or implied by such forward-looking statements. Important factors that could cause or contribute to such differences include risks relating to:

and other factors discussed in our Annual Report on Form 10-K for the year ended December 31, 2019, including in the sections captioned "Risk Factors and Forward Looking Statements. Forward-looking statements speak only as of the date on which they are made, and we assume no obligation to update or revise any forward-looking statements or other information contained herein, whether as a result of new information, future events or otherwise. You are cautioned not to put undue reliance on these forward-looking statements.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200501005015/en/

Original post:
New Data For Teva AJOVY (fremanezumab-vfrm) Injection and AUSTEDO (deutetrabenazine) Tablets Included in Neurology - BioSpace

DetailsCategory: AntibodiesPublished on Friday, 01 May 2020 15:04Hits: 156

Recommendation for approval based on results from pivotal Phase 3 MEDALIST and BELIEVE studies

PRINCETON, NJ & CAMBRIDGE, MA, USA I April 30, 2020 IBristol Myers Squibb (NYSE: BMY) and Acceleron Pharma Inc. (NASDAQ: XLRN) today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has issued a positive opinion, recommending the approval of Reblozyl (luspatercept) for the treatment of:

This CHMP recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines for the European Union (EU). If approved, Reblozyl would be the first erythroid maturation agent approved in the EU, representing a new class of therapy for eligible patients. The safety and efficacy results provided in the application are from the pivotal Phase 3 MEDALIST and BELIEVE studies, evaluating the ability of Reblozyl to effectively address anemia associated with MDS and beta thalassemia, respectively.

"Patients with myelodysplastic syndromes who experience anemia have limited treatment options, and some have been shown to not respond to available erythropoietin-based therapies," said Uwe Platzbecker, M.D., Head of Clinic and Policlinic for Hematology and Cell Therapy, Leipzig University Hospital and lead investigator of the MEDALIST study. If approved, the introduction of a new class of therapy in Reblozyl could provide a promising option to help relieve patients from the burden of regular transfusions to manage their disease.

Todays positive CHMP opinion of Reblozyl is an important milestone for adult beta thalassemia patients in the EU who have limited treatment options to address anemia, a serious consequence of the disease, said Maria Domenica Cappellini, M.D., Professor of Medicine, University of Milan, Fondazione IRCCS Ca Granda and lead investigator of the BELIEVE study. Reblozyl has the potential to significantly decrease the number of red blood cell transfusions patients need.

This decision by the CHMP is an important step towards making this first-in-class therapy an option for eligible patients with anemia due to beta thalassemia or myelodysplastic syndromes, said Diane McDowell, M.D., vice president, Hematology Global Medical Affairs, Bristol Myers Squibb. We, and our partners at Acceleron, look forward to the opportunity to make this treatment option available in the EU and are extremely appreciative of the patients, families and individuals who continue to help us progress important research in a range of serious diseases.

About MEDALIST

MEDALIST is a Phase 3, randomized, double-blind, placebo-controlled, multi-center study evaluating the safety and efficacy of luspatercept plus best supportive care (BSC) versus placebo plus BSC in adults with IPSS-R-defined very low-, low- or intermediate-risk non-del(5q) myelodysplastic syndromes (MDS). All patients were red blood cell (RBC) transfusion-dependent and were either refractory or intolerant to prior erythropoiesis stimulating agent (ESA) therapy, or were ESA nave and unlikely to respond due to endogenous serum erythropoietin levels of 200 U/L, and had no prior treatment with disease modifying agents. Results of the MEDALIST trial were first presented during the Plenary Session of the 2018 American Society of Hematology (ASH) Annual Meeting and were selected for the Best of ASH. The New England Journal of Medicine published the MEDALIST trial results in January 2020.

About MDS

MDS are a group of closely related blood cancers characterized by ineffective production of healthy red blood cells, white blood cells and platelets, which can lead to anemia and frequent or severe infections. People with MDS who develop anemia often require regular blood transfusions to increase the number of healthy red blood cells in circulation. Frequent transfusions are associated with an increased risk of iron overload, transfusion reactions and infections. There are approximately 50,000 patients with MDS in the EU5 countries.

About BELIEVE

BELIEVE is a Phase 3, randomized, double-blind, placebo-controlled multi-center study comparing luspatercept plus BSC versus placebo plus BSC in adults who require regular RBC transfusions (6-20 RBC units per 24 weeks with no transfusion-free period greater than 35 days during that period) due to beta thalassemia. Results of the BELIEVE trial were first presented at the 2018 ASH Annual Meeting and selected for the Best of ASH. The New England Journal of Medicine published the BELIEVE trial results in March 2020.

About Beta Thalassemia

Beta thalassemia is an inherited blood disorder caused by a genetic defect in hemoglobin. The disease is associated with ineffective erythropoiesis, which results in the production of fewer and less healthy RBCs, often leading to severe anemia a condition that can be debilitating and can lead to more severe complications for patients as well as other serious health issues. Treatment options for anemia associated with beta thalassemia are limited, consisting mainly of frequent RBC transfusions that have the potential to contribute to iron overload, which can cause serious complications such as organ damage. Across the United States, Germany, France, Italy, Spain and the United Kingdom, there are approximately 17,000 patients with beta thalassemia.

About Reblozyl

Reblozyl (luspatercept-aamt), a first-in-class erythroid maturation agent, promotes late-stage red blood cell maturation in animal models. Bristol Myers Squibb and Acceleron are jointly developing Reblozyl as part of a global collaboration. Reblozyl is currently approved in the U.S. for the treatment of:

Reblozyl is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia.

Please see full Prescribing Information for REBLOZYL

Bristol Myers Squibb: Advancing Cancer Research

At Bristol Myers Squibb, patients are at the center of everything we do. The goal of our cancer research is to increase patients quality of life, long-term survival and make cure a possibility. We harness our deep scientific experience, cutting-edge technologies and discovery platforms to discover, develop and deliver novel treatments for patients.

Building upon our transformative work and legacy in hematology and Immuno-Oncology that has changed survival expectations for many cancers, our researchers are advancing a deep and diverse pipeline across multiple modalities. In the field of immune cell therapy, this includes registrational chimeric antigen receptor (CAR) T-cell agents for numerous diseases, and a growing early-stage pipeline that expands cell and gene therapy targets, and technologies. We are developing cancer treatments directed at key biological pathways using our protein homeostasis platform, a research capability that has been the basis of our approved therapies for multiple myeloma and several promising compounds in early to mid-stage development. Our scientists are targeting different immune system pathways to address interactions between tumors, the microenvironment and the immune system to further expand upon the progress we have made and help more patients respond to treatment. Combining these approaches is key to delivering new options for the treatment of cancer and addressing the growing issue of resistance to immunotherapy. We source innovation internally, and in collaboration with academia, government, advocacy groups and biotechnology companies, to help make the promise of transformational medicines a reality for patients.

About Bristol Myers Squibb

Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.

Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol-Myers Squibb Company and Juno Therapeutics, a Bristol-Myers Squibb Company.

About Acceleron

Acceleron is a biopharmaceutical company dedicated to the discovery, development, and commercialization of therapeutics to treat serious and rare diseases. The Company's leadership in the understanding of TGF-beta superfamily biology and protein engineering generates innovative compounds that engage the body's ability to regulate cellular growth and repair.

Acceleron focuses its research and development efforts in hematologic and pulmonary diseases. In hematology, Acceleron and its global collaboration partner, Bristol Myers Squibb, are co-promoting REBLOZYL (luspatercept-aamt), the first and only approved erythroid maturation agent, in the United States and are developing luspatercept for the treatment of chronic anemia in myelofibrosis. Acceleron is developing sotatercept for the treatment of pulmonary arterial hypertension, having recently reported positive topline results of the Phase 2 PULSAR trial and actively enrolling patients in the Phase 2 SPECTRA trial.

For more information, please visit http://www.acceleronpharma.com. Follow Acceleron on Social Media: @AcceleronPharma and LinkedIn.

SOURCE: Bristol-Myers Squibb

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Reblozyl (luspatercept) Receives Positive CHMP Opinion for the Treatment of Adults with Anemia in Beta Thalassemia and Myelodysplastic Syndromes |...

HAMBURG, GERMANY / ACCESSWIRE / April 6, 2020 / Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) today announced that the Company has established a dedicated site for research and development of gene therapy-based projects: Evotec Gene Therapy (Evotec GT) which will start operations with a strong team of gene therapy experts at an R&D site in Orth/Donau, Austria.

Evotec GT is an integral part of Evotecs integrated drug discovery platform and complements the Companys existing expertise. This strategic addition marks an important step towards Evotecs long-term vision of becoming a fully modality-agnostic drug discovery and development partnership company.

The team in Austria have worked together for many years and applied their research within gene therapy to different gene therapy-related technologies as well as various indications. The scientists have deep expertise in vectorology and virology as well as disease insights, in particular in hemophilia, hematology, metabolic and muscle diseases. Evotec GTs fully operational site will enable the Company to perform dedicated services in the field of gene therapy along the value chain of its customers from Pharma and biotech as well as foundations and academia.

Dr Werner Lanthaler, Chief Executive Officer of Evotec, commented: We are delighted to initiate our new gene therapy platform and step into this field, which perfectly fits into our business strategy going forward. In recent years, precision medicines based on cell and gene therapies have emerged and are predicted to grow significantly. Gene therapy is a promising approach in the development of genetic medicines for patients, especially for inherited and rare diseases. Finding the best candidate agnostic of modality for any given disease biology will ultimately bring forward the best medicine for patients.

Dr Friedrich Scheiflinger, EVP Head of Gene Therapy at Evotec, said: We are proud to join the growing Evotec team to add the highly promising modality of gene therapy to drug discovery projects. Our team has performed research in the field across different technologies and therapeutic areas for many years and we look forward to leveraging our expertise as part of the truly impressive, modality-agnostic Evotec platform.

About Gene Therapy

Gene therapy is a technique that modifies a persons genes to treat or prevent disease by introduction, removal or editing of genetic material, specifically DNA or RNA, within the cells of a patient. Gene therapies aim to replace a disease-causing gene with a healthy copy, inactivate a disease-causing gene, introduce a new or modified gene or interfere on an expression-regulatory level to support treatment of a disease. Through this modification of gene expression, gene therapies can increase levels of disease-fighting proteins or reduce levels of disease-causing proteins within the cell. Since direct insertion of genes into cells is still very inefficient, gene delivery is facilitated by vehicles which are most often of viral origin. The structure of these viral vectors has been modified to accommodate for the therapeutic gene and to render the vector non-infectious. Depending on the indication and the affected tissue, the technique can be either applied ex-vivo or in-vivo, i.e. with or without removing the cells from the patients body for the therapeutic procedure.

According to various analyst reports, the gene therapy market was valued at approx. $ 500 m in 2018 and the market is expected to reach > $ 5 bn by 2025 with an impressive CAGR of ~34% over the forecast period. Furthermore, rapid and significant progress in the molecular and cellular biology arena, driven by technological advancements in genomics and gene-editing tools, has contributed to an increasing number of approved gene therapies as well as an expanding pipeline. According to the Alliance for Regenerative Medicine (ARM), by the end of the second quarter of 2019, there were more than 700 clinical trials ongoing globally.[1]

ABOUT EVOTEC SE Evotec is a drug discovery alliance and development partnership company focused on rapidly progressing innovative product approaches with leading pharmaceutical and biotechnology companies, academics, patient advocacy groups and venture capitalists. We operate worldwide and our more than 3,000 employees provide the highest quality stand-alone and integrated drug discovery and development solutions. We cover all activities from target-to-clinic to meet the industrys need for innovation and efficiency in drug discovery and development (EVT Execute). The Company has established a unique position by assembling top-class scientific experts and integrating state-of-the-art technologies as well as substantial experience and expertise in key therapeutic areas including neuronal diseases, diabetes and complications of diabetes, pain and inflammation, oncology, infectious diseases, respiratory diseases, fibrosis, rare diseases and womens health. On this basis, Evotec has built a broad and deep pipeline of approx. 100 co-owned product opportunities at clinical, pre-clinical and discovery stages (EVT Innovate). Evotec has established multiple long-term alliances with partners including Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, CHDI, Novartis, Novo Nordisk, Pfizer, Sanofi, Takeda, UCB and others. For additional information please go to http://www.evotec.com and follow us on Twitter @Evotec.

FORWARD LOOKING STATEMENTS Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgement of Evotec as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

Contact Evotec SE:

Gabriele Hansen, SVP Corporate Communications, Marketing & Investor Relations, Phone: +49.(0)40.56081-255,

[1] Sources: https://www.grandviewresearch.com/industry-analysis/gene-therapy-market; https://www.marketwatch.com/press-release/at-339-cagr-gene-therapy-market-size-to-surpass-usd-518-billion-by-2025-2019-09-16; https://www.prnewswire.com/news-releases/gene-therapy-market-to-garner-6-21-bn-globally-by-2026-at-34-8-cagr-says-allied-market-research-300975194.html

SOURCE: Evotec AG via EQS Newswire

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Evotec Expands into Gene Therapy - Associated Press

Q. You and Burns have worked together in the past. Could you describe the collaborative process of turning a book into a documentary?

A. First of all, its an incredible collaboration. When Ken and I launch a film we begin with talks about the book, both of us excited and aware that we are wading into the unknown. We take long walks through Central Park and ask questions outside the nitty gritty of the film: What is the mood of the film? What are the primary messages were trying to convey? I was lucky to work on The Gene with largely the same production team that adapted my first book, The Emperor of All Maladies: A Biography of Cancer, including the incredible filmmaker Barak Goodman (JRN86).

A film is different from a book. In The Gene we wereable to include a trove of historical footage and humanize the inspiring stories of patients and their families seeking cures for their genetic disease. People like Nancy Wexler, professor of neuropsychology at Columbias medical center, who has spent most of her life on an odyssey to find the gene for Huntingtons, a disease that killed her mother. Luke Rosen and Sally Jackson, parents on a tireless quest to raise awareness for their daughters rare degenerative disease. These personal stories help genetics come to life, but they also highlight how much we still do not know. I hope people will find the mood of our film somber, thoughtful and hopeful.

Q. For $200 a person can order a profile of his or her genome that provides ancestral information, as well as genetic health risks. Do you see this as a positive societal development?

A. The question you have to ask is do we want to live in a world where you can send a sample of saliva and find out that you have a 10 percent or 20 percent risk of developing breast cancer in the next 30 years. This information can be useful, motivating you to adopt more positive health behaviors. But it also marks you, changes you. It can change your relationship with yourself, your body. When you decide to test for future risk you are also, inevitably, asking yourself, what kind of future am I willing to risk?

Q. Could genetics play a role in how vulnerable a person is to contracting COVID-19, and whether that person is more at risk of dying from the illness?

A. This is one of the great mysteries of this infection. Young, healthy people are dying, even if most serious cases occur in the elderly and those with pre-existing conditions. There are multiple studies trying to unravel why some people infected with SARS-Cov2, the virus that causes COVID-19, fall seriously ill, while others show only mild or nonexistent symptoms.We are finding a correlation between high viral loadthe amount ofvirus present in any sample taken from a patientand more severe illness.

As I argued recently in The New Yorker, we have done a good job measuring the spread of the virus across populations, but it is now time we learn more about how SARS-Cov2 behaves in the body. This requires large-scale efforts to collect the DNA of people and the virus that they are infected with. One example of a study might be taking the DNA of those with serious underlying disease and comparing it to the DNA of those with mild or asymptomatic cases. We need to determine whether genetic variations among humans affect how susceptible individuals are to COVID-19 infections as rapidly as possible.

Q. What would you like audiences will take away from the film?

A. We hope The Gene will help people understand that the story of the revolution in genetics that is transforming medical science is also the story of what makes us who we are. Wed like to see the film spark a national conversation. The National Institute of Healths National Human Genome Research Institute, our outreach and education partner, is planning many activities. We are in conversations with people in cities across the country, including policymakers and science educators, right down to the primary school level, to take part in discussions and host screenings.

In the next few weeks NIH will launch an interactive digital platform that will go beyond the book and film, adding discussion of the COVID-19 pandemic. After you watch the film, please keep up with us on Twitter to learn more about these activities. Visit @DrSidMukherjee, @KenBurns and @WETA (our producing public media station). Stay tuned.

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Siddhartha Mukherjee and Ken Burns Present PBS Premiere of 'The Gene: An Intimate History' - Columbia University

The coronavirus pandemic has hit older people far harder than those who are younger, but scientists are yet to fully understand why this is.

Many of the elderly people who have died have had pre-existing health conditions such as heart disease, lung disease and diabetes, all of which make fighting the virus more difficult, but many have not had any such health problems, and occasionally the virus has caused the deaths of younger, apparently healthy people.

Researchers around the world are racing to learn how the virus behaves, which health factors put people most at risk, and are trying to work out whether there may be genetic traits that could mean some people respond to the infection differently to others.

Sharing the full story, not just the headlines

There are various theories to suggest why the virus is so unusually and devastatingly selective.

Some scientists have suggested the greater the amount of virus that infects an individual known as the viral load could make a large difference to how the body is able to respond to infection.

Put simply,the larger the dose of the virus a person gets, the worse the infection is, and the least promising the outcome.

A parallel school of thought is that genetic variations between humans differences in our DNA could affect how susceptible an individual is to the virus.

And another candidate for why apparently healthy young people are dying is they may have a highly reactive immune system, which is sent into overdrive fighting off the virus. In such a scenario, a huge inflammation storm could inadvertently overwhelm vital organs such as the lungs.

None of the theories compete with one another, and aspects of all of them, as well as innumerable other factors, could be at play in an individual case.

Viral load

No hype, just the advice and analysis you need

Dr Edward Parker of the London School of Hygiene and Tropical Medicine, explained how a high viral load can impact humans. He said: After we are infected with a virus, it replicates in our bodys cells. The total amount of virus a person has inside them is referred to as their viral load. For Covid-19, early reports from China suggest the viral load is higher in patients with more severe disease, which is also the case for Sars and influenza.

The amount of virus we are exposed to at the start of an infection is referred to as the infectious dose. For influenza, we know that that initial exposure to more virus or a higher infectious dose appears to increase the chance of infection and illness. Studies in mice have also shown that repeated exposure to low doses may be just as infectious as a single high dose.

He added: So all in all, it is crucial for us to limit all possible exposures to Covid-19, whether these are to highly symptomatic individuals coughing up large quantities of virus or to asymptomatic individuals shedding small quantities. And if we are feeling unwell, we need to observe strict self-isolation measures to limit our chance of infecting others.

Professor Wendy Barclay, the head of the Department of Infectious Disease at Imperial College London, said existing knowledge of viral load means healthcare workers can be at greater risk of infection.

In general with respiratory viruses, the outcome of infection whether you get severely ill or only get a mild cold can sometimes be determined by how much virus actually got into your body and started the infection off. Its all about the size of the armies on each side of the battle, a very large virus army is difficult for our immune systems army to fight off.

So standing further away from someone when they breathe or cough out virus likely means fewer virus particles reach you and then you get infected with a lower dose and get less ill. Doctors who have to get very close to patients to take samples from them or to intubate them are at higher risk so need to wear masks.

Genetic differences between those infected

Scientists are currently preparing to scour Covid-19 patients genomes for DNA variations that might indicate why some people are more at risk than others.

The findings could then be used to identify groups most at risk of serious illness and those who might be protected, and this knowledge could then inform the hunt for effective treatments.

A huge effort to pool DNA research from patients around the world is now on, with the ultimate goal being to build a body of evidence from people with no underlying health issues, but who have reacted differently to infection by the virus.

One promising strand of research into why some people are more susceptible to the coronavirus is on the gene variation for the cell surface protein angiotensin-converting enzyme 2 (ACE2), found on the outer membranes of cells, and which the coronavirus uses to enter cells in the lungs and airways.

Variations in production of ACE2 could make it easier or more difficult for the virus to enter and infect cells.

We see huge differences in clinical outcomes and across countries. How much of that is explained by genetic susceptibility is a very open question, geneticist Andrea Ganna, of the University of Helsinkis Institute for Molecular Medicine Finland, told Science Magazine.

Another fascinating line of inquiry is whether different blood types could lead to differing levels of susceptibility to the disease.

A Chinese research team reported in a non-peer-reviewed article that people with type O blood may be protected from the virus, and those with type A blood could be at greater risk.

Were trying to figure out if those findings are robust, Stanford University human geneticist Manuel Rivas told Science Magazine.

The first results from the investigations into genetic differences and susceptibility are expected in less than two months time.

Originally posted here:
How 'viral load' and genetics could explain why young people have died from coronavirus - The Independent

SAN RAFAEL, Calif., April 6, 2020 /PRNewswire/ --BioMarin Pharmaceutical Inc.(NASDAQ: BMRN) today announced that based on recent meetings with health authorities in the US and Europe, the Company plans to submit marketing applications to the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) in the third quarter of 2020 for vosoritide.Vosoritide is an investigational, once daily injection analog of C-type Natriuretic Peptide (CNP) for achondroplasia, the most common form of disproportionate short stature in humans.

The marketing applications are based on the outcomes from the randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of vosoritide, announced in Dec 2019, and further supported by the long-term safety and efficacy from the Phase 2 study, ongoing extension studies, and extensive natural history data. If approved, vosoritide would be the first medicine for the treatment of Achondroplasia in the US and Europe.

"We have worked with the regulatory authorities throughout the design and development of our clinical program and look forward to the ongoing interactions in the evaluation of the safety and efficacy of vosoritide in children with achondroplasia," said Hank Fuchs, M.D., President Worldwide Research and Development at BioMarin."We believe that we have a strong data package that combines the gold standard of a randomized, double-blind, placebo-controlled Phase 3 study with the long-term results in the Phase 2 open label study and extensive contemporaneous natural history data to evaluate durability.We are grateful to the children and families who have participated in these studies and are contributing to the greater body of scientific data on a potential treatment for achondroplasia."

"Vosoritide is the first potential pharmacological treatment for the underlying cause of achondroplasia. It could be a medical breakthrough in providing physicians with a new tool to treat individuals with achondroplasia," said John A. Phillips, III, M.D., Vanderbilt University Medical Center (David T Karzon Professor of Pediatrics) and investigator for the vosoritide clinical program. "To have such a possible treatment for achondroplasia on the horizon, where none existed before is significant progress."

"We are making great strides in understanding the biology of skeletal dysplasia and getting closer to a potential treatment," said Klaus Mohnike, Professor of Paediatrics at Magdeburg University Hospital in Germany and investigator for the vosoritide clinical program. "I am looking forward to therapeutic interventions that go beyond treating symptoms and have the potential to make a lasting difference for those affected children."

Vosoritide has received orphan drug designation from the FDA and EMA for the treatment of achondroplasia.The Orphan Drug Designation program is intended to advance the evaluation and development of products that demonstrate promise for the diagnosis and/or treatment of rare diseases or conditions.

Description of Phase 3 Study

The global Phase 3 study was a randomized, double-blind, placebo-controlled study of vosoritide in 121 children with achondroplasia aged 5 to 14 for 52 weeks. (The enrollment age criteria were 5 to 18 per the study protocol).Vosoritide is being tested in children whose growth plates are still open. This is approximately 25% of people with achondroplasia. Children in this study have completed a minimum six-month baseline study to determine their baseline growth velocity prior to entering the Phase 3 study.The primary endpoint of the study was the change in growth velocity from baseline over one year in children treated with vosoritide compared to placebo. A wide range of secondary and exploratory endpoints included anthropometric measures such as height Z-score, body and limb proportionality and joint geometry; biochemical, biomarker and radiological assessments of bone growth and health; and evaluations of health-related quality of life (HRQoL), developmental status, and functional independence.These additional endpoints address the overall impact vosoritide has on achondroplasia and continue to be evaluated in an ongoing open-label extension study where all subjects receive active treatment.

Description of Phase 2 Dose Finding Study

The primary objectives of the open-label, sequential cohort, dose-finding study were to evaluate the safety and tolerability of daily subcutaneous vosoritide and to determine the dose to carry forward to Phase 3. Secondary objectives were to evaluate the effects of vosoritide on change from pre-treatment baseline in annualized growth velocity (cm/year), height Z-scores, and body segment proportionality, the vosoritide pharmacokinetic (PK) profile, and biomarkers of vosoritide activity, and endochondral ossification. All children who completed the 24-month dose finding study were then eligible to continue long term follow up in the ongoing extension study which provides long term evidence of efficacy, durability of effect and safety.

About Achondroplasia

Achondroplasia, the most common form of disproportionate short stature in humans, is characterized by slowing of endochondral ossification, which results in disproportionate short stature and disordered architecture in the long bones, spine, face and base of the skull.This condition is caused by a mutation in the fibroblast growth factor receptor 3 gene (FGFR3), a negative regulator of bone growth. Beyond disproportionate short stature, people with achondroplasia can experience serious health complications, including foramen magnum compression, sleep apnea, bowed legs, mid-face hypoplasia, permanent sway of the lower back, spinal stenosis and recurrent ear infections. Some of these complications can result in the need for invasive surgeries such as spinal cord decompression and straightening of bowed legs. In addition, studies show increased mortality at every age.

More than 80% of children with achondroplasia have parents of average stature and have the condition as the result of a spontaneous gene mutation.The worldwide incidence rate of achondroplasia is about one in 25,000 live births.Vosoritide is being tested in children whose growth plates are still "open," typically those under 18 years of age.This is approximately 25% of people with achondroplasia.In the U.S., Europe, Latin America,the Middle East, and most of Asia Pacific, there are currently no licensed medicines for achondroplasia.

About BioMarin

BioMarin is a global biotechnology company that develops and commercializes innovative therapies for patients with serious and life-threatening rare genetic diseases. The company's portfolio consists of six commercialized products and multiple clinical and pre-clinical product candidates. For additional information, please visit http://www.biomarin.com. Information on such website is not incorporated by reference into this press release.

Forward-Looking Statement

This press release contains forward-looking statements about the business prospects of BioMarin Pharmaceutical Inc. (BioMarin), including, without limitation, statements about: BioMarin's vosoritide development program generally and specifically about the Company's planned submissions for marketing applications in the U.S. to the FDA and in Europe to the EMA, the strength of the data package to be submitted to regulatory authorities, the continued clinical development of vosoritide and the timing and conduct of such clinical program; the possible results of such studies, and the timing of the submissions of marketing applications to health authorities in the U.S. and Europe. These forward-looking statements are predictions and involve risks and uncertainties such that actual results may differ materially from these statements. These risks and uncertainties include, among others: final analysis of the Phase 3 data, results and timing of current and planned preclinical studies and clinical trials of vosoritide; our ability to successfully manufacture vosoritide; the content and timing of decisions by the U.S. Food and Drug Administration, the European Commission and other regulatory authorities concerning vosoritide; and those other risks and uncertainties detailed from time to time under the caption "Risk Factors" and elsewhere in the BioMarin's Securities and Exchange Commission (SEC) filings, including, without limitation, BioMarin's Quarterly Report on Form 10-K for the year ended December 31, 2019, and future SEC filings and reports by BioMarin. BioMarin undertakes no duty or obligation to update any forward-looking statements contained in this press release as a result of new information, future events or changes in its expectations.

BioMarin is a registered trademark of BioMarin Pharmaceutical Inc.

Contacts:

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Debra Charlesworth

BioMarin Pharmaceutical Inc.

BioMarin Pharmaceutical Inc.

(415) 455-7558

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BioMarin Plans Regulatory Submissions for Marketing Authorization of Vosoritide to Treat Children with Achondroplasia in 3Q 2020 in both US and Europe...

COVID-19 is caused by a coronavirus called SARS-CoV-2. Coronaviruses belong to a group of viruses that infect animals, from peacocks to whales. Theyre named for the bulb-tipped spikes that project from the viruss surface and give the appearance of a corona surrounding it.

A coronavirus infection usually plays out one of two ways: as an infection in the lungs that includes some cases of what people would call the common cold, or as an infection in the gut that causes diarrhea. COVID-19 starts out in the lungs like the common cold coronaviruses, but then causes havoc with the immune system that can lead to long-term lung damage or death.

SARS-CoV-2 is genetically very similar to other human respiratory coronaviruses, including SARS-CoV and MERS-CoV. However, the subtle genetic differences translate to significant differences in how readily a coronavirus infects people and how it makes them sick.

SARS-CoV-2 has all the same genetic equipment as the original SARS-CoV, which caused a global outbreak in 2003, but with around 6,000 mutations sprinkled around in the usual places where coronaviruses change. Think whole milk versus skim milk.

Compared to other human coronaviruses like MERS-CoV, which emerged in the Middle East in 2012, the new virus has customized versions of the same general equipment for invading cells and copying itself. However, SARS-CoV-2 has a totally different set of genes called accessories, which give this new virus a little advantage in specific situations. For example, MERS has a particular protein that shuts down a cells ability to sound the alarm about a viral intruder. SARS-CoV-2 has an unrelated gene with an as-yet unknown function in that position in its genome. Think cow milk versus almond milk.

How the virus infects

Every coronavirus infection starts with a virus particle, a spherical shell that protects a single long string of genetic material and inserts it into a human cell. The genetic material instructs the cell to make around 30 different parts of the virus, allowing the virus to reproduce. The cells that SARS-CoV-2 prefers to infect have a protein called ACE2 on the outside that is important for regulating blood pressure.

The infection begins when the long spike proteins that protrude from the virus particle latch on to the cells ACE2 protein. From that point, the spike transforms, unfolding and refolding itself using coiled spring-like parts that start out buried at the core of the spike. The reconfigured spike hooks into the cell and crashes the virus particle and cell together. This forms a channel where the string of viral genetic material can snake its way into the unsuspecting cell.

SARS-CoV-2 spreads from person to person by close contact. The Shincheonji Church outbreak in South Korea in February provides a good demonstration of how and how quickly SARS-CoV-2 spreads. It seems one or two people with the virus sat face to face very close to uninfected people for several minutes at a time in a crowded room. Within two weeks, several thousand people in the country were infected, and more than half of the infections at that point were attributable to the church. The outbreak got to a fast start because public health authorities were unaware of the potential outbreak and were not testing widely at that stage. Since then, authorities have worked hard and the number of new cases in South Korea has been falling steadily.

How the virus makes people sick

SARS-CoV-2 grows in type II lung cells, which secrete a soap-like substance that helps air slip deep into the lungs, and in cells lining the throat. As with SARS, most of the damage in COVID-19, the illness caused by the new coronavirus, is caused by the immune system carrying out a scorched earth defense to stop the virus from spreading. Millions of cells from the immune system invade the infected lung tissue and cause massive amounts of damage in the process of cleaning out the virus and any infected cells.

Each COVID-19 lesion ranges from the size of a grape to the size of a grapefruit. The challenge for health care workers treating patients is to support the body and keep the blood oxygenated while the lung is repairing itself.

How SARS-CoV-2 infects, sickens and kills people.

SARS-CoV-2 has a sliding scale of severity. Patients under age 10 seem to clear the virus easily, most people under 40 seem to bounce back quickly, but older people suffer from increasingly severe COVID-19. The ACE2 protein that SARS-CoV-2 uses as a door to enter cells is also important for regulating blood pressure, and it does not do its job when the virus gets there first. This is one reason COVID-19 is more severe in people with high blood pressure.SARS-CoV-2 is more severe than seasonal influenza in part because it has many more ways to stop cells from calling out to the immune system for help. For example, one way that cells try to respond to infection is by making interferon, the alarm signaling protein. SARS-CoV-2 blocks this by a combination of camouflage, snipping off protein markers from the cell that serve as distress beacons and finally shredding any anti-viral instructions that the cell makes before they can be used. As a result, COVID-19 can fester for a month, causing a little damage each day, while most people get over a case of the flu in less than a week.

At present, the transmission rate of SARS-CoV-2 is a little higher than that of the pandemic 2009 H1N1 influenza virus, but SARS-CoV-2 is at least 10 times as deadly. From the data that is available now, COVID-19 seems a lot like severe acute respiratory syndrome (SARS), though its less likely than SARS to be severe.

What isnt known

There are still many mysteries about this virus and coronaviruses in general the nuances of how they cause disease, the way they interact with proteins inside the cell, the structure of the proteins that form new viruses and how some of the basic virus-copying machinery works.

Another unknown is how COVID-19 will respond to changes in the seasons. The flu tends to follow cold weather, both in the northern and southern hemispheres. Some other human coronaviruses spread at a low level year-round, but then seem to peak in the spring. But nobody really knows for sure why these viruses vary with the seasons.

What is amazing so far in this outbreak is all the good science that has come out so quickly. The research community learned about structures of the virus spike protein and the ACE2 protein with part of the spike protein attached just a little over a month after the genetic sequence became available. I spent my first 20 or so years working on coronaviruses without the benefit of either. This bodes well for better understanding, preventing and treating COVID-19.

[Get facts about coronavirus and the latest research. Sign up for our newsletter.]

Benjamin Neuman, Professor of Biology, Texas A&M University-Texarkana

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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What The Coronavirus Does To Your Body That Makes It So Deadly - IFLScience

Hospitals do not have enough PPEs (personal protective equipment gloves, masks, gowns, shoe coverings), nor sufficient access to COVID-19 testing.

When a policy is made to disallow family members from being with loved ones, it is considered inhumane. Yet, hospitals must protect patients from spreading this virus to the medical staff and the public. One contaminating source could be from visiting family members.

Conversely, ill loved ones need a hand to hold and psychological support to alleviate pain and suffering. We know there are aspects of the mind that modern medicine cannot heal.

The initial solution: Utilize cell phone technology to maintain communication if your hospitalized loved one is capable.

The next solution: Find a way quickly to increase hospital PPE supplies and augment COVID-19 testing.

Once this is done:

Allow at least one garbed family member to be with their loved one;

Educate them on the proper use of PPEs;

Emphasize cleansing techniques like handwashing and keeping the surrounding room sterile;

Get testing for family members as well as staff.

Everyone must be protected and comforted, but lets adapt and find creative solutions to assure continued humanity in hospitals during this crisis.

Gene Uzawa Dorio, M.D., is a geriatric house-call physician who serves as president of the Los Angeles County Commission for Older Adults and Assemblyman to the California Senior Legislature. He has practiced in the Santa Clarita Valley for 32 years.

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Comforting a Loved One | Doctor's Diary with Dr. Gene Dorio - SCVNEWS.com