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April 21st, 2020

Study Shows Glaucoma Might Be Successfully Treated with Gene Therapy Using CRISPR-Cas9 Gene Editing to Inactivate Aquaporin 1 Gene in Ciliary Body That Produces Fluid That Maintains Pressure in Eye; Treatment Lowers Intraocular Pressure in Mouse Model

A new study led by scientists at the University of Bristol in the UK has shown that a common eye condition, glaucoma, might be successfully treated with a single injection using gene therapy, which would improve treatment options, effectiveness, and quality of life for many patients. Glaucoma affects over 64 million people worldwide and is a leading cause of irreversible blindness. It is usually caused by fluid building up in the front part of the eye, which increases pressure inside the eye and progressively damages the nerves responsible for sight. Current treatments include either eye drops, laser, or surgery, all of which have limitations and disadvantages. The research team led by academics at the Bristol Medical School: Translational Health Sciences tested a new approach that might provide additional treatment options and benefits. Their findings were published in the March 4,2020 issue of Molecular Therapy. The open-access article is titled “Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9.” The researchers designed a gene therapy and demonstrated proof of concept using experimental mouse models of glaucoma and human donor tissue. The treatment targeted part of the eye called the ciliary body, which produces the fluid that maintains pressure within the eye. Using the latest gene-editing technology called CRISPR, a gene called Aquaporin 1 in the ciliary body was inactivated leading to reduced eye pressure. Dr Colin Chu, Visiting Senior Research Fellow in the Bristol Medical School: Translational Health Sciences and corresponding author, said: "Currently there is no cure for glaucoma, which can lead to loss of vision if the disease is not diagnosed and treated early.

Study Identifies Potential Drug Treatments for Telomere Diseases Such As Dyskeratosis Congenita, Aplastic Anemia, Liver Cirrhosis, and Pulmonary Fibrosis; Small Compounds Selectively Lengthen Telomeres in Stem Cells

Capping decades of research, a new study may offer a breakthrough in treating dyskeratosis congenita and other so-called “telomere diseases,” in which cells age prematurely. Using cells donated by patients with the disease, researchers at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center identified several small molecules that appear to reverse this cellular aging process. Suneet Agarwal, MD, PhD, the study's senior investigator, hopes at least one of these compounds will advance toward clinical trials. Findings were published online on April 21, 2020 in Cell Stem Cell (https://www.sciencedirect.com/science/article/abs/pii/S1934590920301387?...). If so, it could be the first treatment for dyskeratosis congenita (DC) that could reverse all of the disease's 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 article is titled “Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells.” 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 body's stem cells, which retain their youthful qualities, normally make an enzyme called telomerase that builds telomeres back up again. But when telomeres can't 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.

How SARS-CoV-2 (COVID-19) Gets into Respiratory Tissue -- And How It May Exploit One of Our Anti-Viral Defenses; Interferon Boosts ACE2, Which Is Cell Surface Receptor That COVID-19 Binds To

What makes SARS-CoV-2, the virus behind COVID-19, such a threat? A new study, led by Jose Ordovas-Montanes, PhD at Boston Children's Hospital and Alex K. Shalek, PhD, at MIT, pinpoints the likely cell types the virus infects. Unexpectedly, it also shows that one of the body's main defenses against viral infections may actually help the virus infect those very cells. Findings were published online on April 21, 2020 in Cell (https://www.cell.com/pb-assets/products/coronavirus/CELL_CELL-D-20-00767...). The peer-reviewed study, published as a preprint, will help focus efforts to understand what SARS-COV-2 does in the body, why some people are more susceptible, and how best to search for treatments, the researchers say. The pre-print is titled “SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene In Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets Across Tissues.” When news broke about a new coronavirus in China, Dr. Ordovas-Montanes and Dr. Shalek had already been studying different cell types from throughout the human respiratory system and intestine. They also had gathered data from primates and mice. In February, they began diving into these data. "We started to look at cells from tissues such as the lining of the nasal cavity, the lungs, and gut, based on reported symptoms and where the virus has been detected," says Dr. Ordovas-Montanes. "We wanted to provide the best information possible across our entire spectrum of research models." Recent research had found that SARS-CoV-2--like the closely related SARS-CoV that caused the SARS pandemic--uses a receptor called ACE2 (angiotensin-converting enzyme 2) to gain entry into human cells, aided by an enzyme called TMPRSS2 (transmembrane serine protease 2). That led Dr. Ordovas-Montanes and Dr.

Diagnostic Biosensor Detects SARS-CoV-2 (COVID-19) from Nasopharyngeal Swabs in Less Than Minute

According to many experts, early diagnosis and management are critical for slowing the spread of SARS-CoV-2, the new coronavirus that causes COVID-19. Therefore, the race is on to develop diagnostic tests for the virus that are faster, easier and more accurate than existing ones. Now, researchers, reporting online on April 15, 2020 in ACS Nano, have developed a field-effect transistor-based biosensor that detects SARS-CoV-2 in nasopharyngeal swabs from patients with COVID-19, in less than one minute. The open-access article is titled “Rapid Detection of COVID-19 Causative Virus (SARS-CoV-2) in Human Nasopharyngeal Swab Specimens Using Field-Effect Transistor-Based Biosensor,” Currently, most diagnostic tests for COVID-19 rely on a technique called real-time reverse transcription-polymerase chain reaction (RT-PCR), which amplifies DNA that has been produced by reverse transcription from SARS-CoV-2 RNA from patient swabs so that tiny amounts of the virus can be detected. However, the method takes at least 3 hours, including a step to prepare the viral RNA for analysis. Edmond Changkyun Park, PhD, and Seung Il Kim, PhD, both at the Korea Basic Science Institute in the Republic of Korea, and colleagues, wanted to develop a faster diagnostic test that could analyze patient samples directly from a tube of buffer containing the swabs, without any sample preparation steps. The team based its test on a field-effect transistor -- a sheet of graphene with high electronic conductivity. The researchers attached antibodies against the SARS-CoV-2 spike protein to the graphene. When they added either purified spike protein or cultured SARS-CoV-2 virus to the sensor, binding to the antibody caused a change in the electrical current.

Rare Enigmatic South American Ground Beetle Sports Unusual, Likely Multi-Purpose, “Antennal Cleaners”

For 157 years, scientists have wished they could understand the evolutionary relationships of a curious South American ground beetle that was missing a distinctive feature of the huge family of ground beetles (Carabidae). Could it be that this rare species was indeed lacking a characteristic trait known in over 40,000 species worldwide and how could that be? Was that species assigned to the wrong family from the very beginning? The species, Nototylus fryi, or Fry's strange-combed beetle, is known so far only from a single, damaged specimen, found in 1863 in the Brazilian State of Espíritu Santo, that today is kept in the Natural History Museum of London. So rare and unusual, due to its lack of "antennal cleaners" - specialized "combing" structures located on the forelegs and used by carabids to keep their antennae clean, it also prompted the description of its own genus: Nototylus, now colloquially called “strange-combed beetles.” No mention of the structure was made in the original description of the species, so, at one point, scientists even started to wonder whether the beetle they were looking at was in fact a carabid at all. Because the area where Fry's strange-combed beetle had been found was once Southern Atlantic Forest, but today is mostly sugar cane fields, cacao plantations, and cattle ranches, scientists have feared that additional specimens of strange-combed beetles might never be collected again and that the group was already extinct. Recently, however, a US team of entomologists has reported the discovery of a second specimen, one also representing a second species of strange-combed beetles new to science.

April 19th

First COVID-19 Patient Treated with Inhaled Nitric Oxide Therapy; Prior Studies Have Shown NO May Prevent Viral Replication, Improve Arterial Oxygenation, Reduce Need for Ventilation Support, & Prevent Proliferation of Lung Infiltrates

On March 30, 2020, Bellerophon Therapeutics, Inc. (Nasdaq: BLPH), a clinical-stage biotherapeutics company focused on developing treatments for cardiopulmonary diseases, announced that emergency expanded access treatment with its INOpulse(R) inhaled nitric oxide (iNO) system (iNO) was initiated for the first time in a patient with a diagnosis of the novel coronavirus disease COVID-19 at the University of Miami School of Medicine. The treatment follows the recent decision by the U.S. Food and Drug Administration (FDA) to grant emergency expanded access that allows INOpulse to be used immediately for the treatment of COVID-19 under the care and supervision of the patient’s physician. "Based on previous studies that demonstrate the benefits of iNO in oxygenation and immune response, INOpulse has the potential to be used as a viable treatment option for COVID-19," said the treating physician, Roger Alvarez, DO, MPH, Assistant Professor, University of Miami School of Medicine. "The cardiopulmonary benefit demonstrated by INOpulse in various indications provides the potential to prevent deterioration in patients with COVID-19, allowing ventilators to be preserved for the most critically ill. INOpulse's ease of administration could significantly decrease the burden on therapists and nurses as they combat this pandemic with constrained resources." NO is a molecule naturally produced in the endothelial lining of blood vessels that plays a significant role in vasodilation, or opening of the arteries, including arteries in the lung.

April 19th

Rockefeller University Launches Broad Range of Studies on COVID-19

Rockefeller University experts in infectious disease, immunology, biochemistry, structural biology, and genetics have begun over a dozen projects in recent weeks aimed at better understanding the biology of the SARS-CoV-2 virus, which is responsible for the current global COVID-19 pandemic. The research, which involves 18 laboratories and over 130 scientists, has the goal of discovering or developing new, urgently needed approaches to prevent and treat the disease. Although most Rockefeller laboratories have ceased on-campus operations to reduce the spread of the illness, exceptions have been made for those researchers working on essential COVID-19-related projects. Because the development, scale-up, and deployment of a safe and effective vaccine for the virus are still well over the horizon, the researchers are focusing on parallel approaches to provide alternative means of prevention and therapy, attacking the problem from many angles. Projects include the development of antibodies and other protein therapeutics capable of preventing or treating the infection; development of small molecules that inhibit the activity of viral or human proteins that are required for viral replication; improved animal models for testing potential treatments; and identification of new vulnerabilities of the virus via both genomic studies of humans with unusual sensitivity or resistance to infection, and cell-based screens using CRISPR gene-editing technology. “These projects directly relate to pathophysiology, prevention, and treatment of COVID-19, as well as the basic biology of the SARS-CoV-2 virus itself,” says Richard P. Lifton, MD, PhD, the university’s president.

MIT Scientists Design Water-Soluble, Modified Cytokine Receptors That Can Bind Cytokines; New Molecules May Prove Useful in Treating “Cytokine Storms” Associated with COVID-19 and Other Infections

One of the defining features of Covid-19 is the excessive immune response that can occur in severe cases. This burst of immune over-reaction, also called a cytokine storm, damages the lungs and can be fatal. A team of MIT researchers has developed specialized proteins, similar in structure to antibodies, that they believe could soak up these excess cytokines. “The idea is that they can be injected into the body and bind to the excessive cytokines as generated by the cytokine storm, removing the excessive cytokines and alleviating the symptoms from the infection,” says Rui Qing, PhD, an MIT research scientist who is one of the senior authors of the study. The researchers have reported their initial findings in Quarterly Review of Biophysics (QRB) Discovery, and they now hope to begin testing their proteins in human cells and in animal models of cytokine release and coronavirus infection. The article is titled “QTY Code-Designed Water-Soluble Fc-Fusion Cytokine Receptors Bind to Their Respective Ligands.” Shuguang Zhang, PhD, a principal research scientist in the MIT Media Lab’s Laboratory of Molecular Architecture, is also a senior author of the paper. Shilei Hao, PhD, a visiting scientist at MIT, is the lead author of the study, and David Jin, MD, PhD, CEO and President of Avalon GloboCare, is also an author. The researchers’ work on blocking cytokine storms grew out of a project that Dr. Zhang began ten years ago to develop modified versions of membrane-embedded proteins. These proteins are usually difficult to study because once they are extracted from the cell membrane, they only maintain their structure if they are suspended in special types of detergents. After working on the problem for several years, Dr. Zhang and Dr.

Princeton Researchers Design Shorter Promoters for Gene Delivery of Larger or Multiple Genes in Gene Therapy for Neurological Diseases; New Promoters Can Keep Transferred Genes Active for Long Periods of Time

A recently developed system for switching on the activity of genes could improve treatments for a broad range of neurological diseases. Esteban Engel, PhD, a researcher in viral neuroengineering in the Princeton Neuroscience Institute at Princeton University and Director of the Institute’s Viral Core Facility, and his team have developed new gene promoters, which act like switches to turn on gene expression, that promise to broaden the ability to deliver large genes and keep them active for long periods of time. The research was published online on April 14, 2020 in Molecular Therapy: Methods & Clinical Development. The open-access article is titled “Small Alphaherpesvirus Latency-Associated Promoters Drive Efficient and Long-Term Transgene Expression in the Central Nervous System.” [Please see video describing this work in press release at (https://www.eurekalert.org/pub_releases/2020-04/pu-nta041720.php)]. The team is developing these genetic switches for use in gene therapy, the practice of delivering new genes to replace or assist ones that are faulty. Gene therapy is a promising strategy for many diseases, including disorders that involve the brain, such as Parkinson's disease and Alzheimer's disease. To carry genes into cells, scientists take advantage of the fact that viruses come equipped with the machinery to gain entry to cells. Over the years, scientists have engineered viruses to deliver genes in ways that are safe and don't cause disease. One of the viruses commonly used for this is the relatively harmless adeno-associated virus (AAV). Dr. Engel and his team created new gene promoters that turn on genes after they have been transported into neurons, the cells of the brain and nervous system.

April 18th

ReNeuron Announces Exosome Research Collaboration; Agrees to Produce Exosomes for the Delivery of Gene-Silencing Sequences

On April 7, 2020, ReNeuron Group plc (AIM: RENE), a UK-based global leader in the development of cell-based therapeutics, announced that it has signed a research agreement with an unnamed major pharmaceutical company to explore the potential use of the Company's proprietary exosomes to deliver novel therapeutics. The agreement follows the Company's strategy of collaborating with pharmaceutical and biotechnology companies to use its exosome technology as a novel delivery vehicle. ReNeuron's exosomes are derived from its CTX neural stem cell line and have the ability to cross the blood brain barrier and to be manufactured at scale. The research collaboration will focus on the use of the Company's exosomes for the delivery of gene silencing sequences created by the pharmaceutical company. ReNeuron will be responsible for manufacturing exosomes and then loading them with the gene silencing sequences after which the pharmaceutical company will evaluate the loaded exosomes. ReNeuron will be paid by the pharmaceutical company for manufacturing and loading the exosomes in the initial phase of the collaboration. This is ReNeuron's second research collaboration following the signing of an ongoing agreement with a U.S. pharmaceutical company in January 2019. "We are delighted to have signed this latest exosome research collaboration agreement with an experienced leader in the discovery and development of novel gene silencing-based therapeutics," commented Olav Hellebø, MBA, Chief Executive Officer of ReNeuron.