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Archive - Apr 2020


April 22nd

Pre-Existing Diabetes Reversed in Mice Using Genetically-Edited Stem Cells (iPSCs) Derived from Patient with Wolfram Syndrome, a Form of Diabetes Caused by Mutations in Single Gene; CRISPR Corrects Genetic Defect So Cells Can Normalize Blood Sugar

Using induced pluripotent stem cells (iPSCs) produced from the skin of patients with a rare, monogenic form of insulin-dependent diabetes called Wolfram syndrome, researchers transformed the human stem cells into insulin-producing cells and used the gene-editing tool CRISPR/Cas9 to correct the genetic defect that had caused the syndrome. They then implanted the cells into lab mice with streptozocin-induced diabetes and cured the generally unrelenting diabetes in those mice. The findings, from researchers at Washington University School of Medicine in St. Louis suggest the CRISPR/Cas9 technique may hold promise as a treatment for diabetes, particularly the forms caused by a single gene mutation, and it also may be useful one day in some patients with the more common forms of diabetes, such as type 1 and type 2. The study was published online on April 22, 2020 in Science Translational Medicine. The article is titled “Gene-Edited Human Stem Cell-Derived ß Cells from a Patient with Monogenic Diabetes Reverse Pre-Existing Diabetes in Mice.” Patients with Wolfram syndrome develop diabetes during childhood or adolescence and quickly require insulin-replacement therapy, requiring insulin injections multiple times each day. Most go on to develop problems with vision and balance, as well as other issues, and in many patients, the syndrome contributes to an early death. "This is the first time CRISPR has been used to fix a patient's diabetes-causing genetic defect and successfully reverse diabetes," said co-senior investigator Jeffrey R. Millman, PhD, an Assistant Professor of Medicine and of Biomedical Engineering at Washington University School of Medicine. "For this study, we used cells from a patient with Wolfram syndrome because, conceptually, we knew it would be easier to correct a defect caused by a single gene.

MIT Scientists & Colleagues Identify Cells Likely Targeted by COVID-19 Virus: Specific Cells in Nasal Passages, Lungs, and Intestines; Team Also Shows That Interferon Activates ACE2 Receptor That CORVID-19 Binds to Gain Entry to Cells

Researchers at MIT; the Broad Institute of MIT and Harvard; and the Ragon Institute of MGH, MIT, and Harvard; along with colleagues from around the world, have identified specific types of cells that appear to be targets of the coronavirus that is causing the COVID-19 pandemic. Using existing data on the RNA found in different types of cells, the researchers were able to search for cells that express the two proteins (ACE2 & TMRSS) that help the SARS-CoV-19 virus enter human cells. They found subsets of cells in the lung, the nasal passages, and the intestine that express RNA for both of these proteins much more than other cells. The researchers hope that their findings will help guide scientists who are working on developing new drug treatments or testing existing drugs that could be repurposed for treating COVID-19. "Our goal is to get information out to the community and to share data as soon as is humanly possible, so that we can help accelerate ongoing efforts in the scientific and medical communities," says Alex K. Shalek, PhD, the Pfizer-Laubach Career Development Associate Professor of Chemistry at MIT, a core member of MIT's Institute for Medical Engineering and Science (IMES), an extramural member of the Koch Institute for Integrative Cancer Research, an associate member of the Ragon Institute, and an institute member at the Broad Institute. Dr. Shalek and Jose Ordovas-Montanes, PhD, a former MIT postdoc who now runs his own lab at Boston Children's Hospital, are the senior authors of the study, which was published online on April 21, 2020 in Cell (

April 21st

Scripps Research Expands International Effort to Rapidly Repurpose Existing Drugs Against COVID-19 Using Calibr’s ReFRAME Drug Repurposing Collection (>14,000 Compounds); “It’s Fantastic Resource for the Scientific Community,” Says HIV Virologist David Ho

With the COVID-19 pandemic continuing to spread around the globe, Scripps Research has quickly established an international network of collaborating scientific laboratories to leverage ReFRAME, the world’s leading drug repurposing collection, to find antiviral compounds against the novel coronavirus, according to April 16, 2020 release from Scripps Research. Researchers at Calibr, the Drug Development Division of Scripps Research, are teaming up with scientists from the United States, Europe, and Asia to screen the vast collection of compounds for individual drugs or combinations that may be effective in treating people exposed to COVID-19. “COVID-19 is an unprecedented public health crisis that will only be brought fully under control by effective medical therapies,” said Peter Schultz, PhD, President and CEO of Scripps Research. “Repurposing drugs that have already been approved for use in humans, or compounds for which we have ample safety data, offers the most rapid path to finding an antiviral drug or drug combination that is effective against COVID-19.” Calibr established the ReFRAME collection in 2018 with support from the Bill & Melinda Gates Foundation to tackle areas of urgent unmet medical need, especially neglected tropical diseases. The collection has since grown to comprise over 14,000 compounds, including drugs that are already being repurposed for a number of diseases. Calibr also developed an open source database containing preclinical and clinical data on these drugs. With such well-characterized therapeutic properties, the compounds can be rapidly screened and advanced into a patient setting, without many of the steps typically required for new drugs to reach that stage.

April 21st

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 ( 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 ( 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.