Camostat Mesilate

Transmission electron micrograph of a SARS-CoV-2 virus particle isolated from a patient. Credit: NIAID. The National Institutes of Health (NIH) has commenced subject enrolment in a Phase II/III ACTIV-2 trial of a new fully human polyclonal antibody therapeutic called SAB-185 for treating Covid-19 in non-hospitalised individuals with mild or moderate disease. Developed by SAB Biotherapeutics, SAB-185 has shown to neutralise live SARS-CoV-2 at titers higher than convalescent plasma in pre-clinical studies. Funded by the NIH unit National Institute of Allergy and Infectious Diseases, ACTIV-2 is a master protocol to assess various investigational agents in people with mild-to-moderate Covid-19 who do not require hospitalisation. The ACTIV-2 study design aids scientists in analysing SAB-185 in a small subject group and then progress it to a larger group on finding that the antibody is safe and effective. In the trial, participants will randomly be given either intravenous SAB-185 or another therapeutic or a placebo. Other therapeutics being analysed in the trial are Brii Biosciences’ experimental antibodies, BRII-196 and BRII-198, Synairgen’s SNG001, AstraZeneca’s AZD7442, and Sagent Pharmaceuticals’ Camostat mesilate. The blinded Phase II study will enrol 110 subjects with mild or moderate Covid-19 and are at risk for disease progression. On finding no serious safety concerns and with promising results from the Phase II study, the trial will progress to Phase III. The Phase III study intends to enrol 421 additional subjects who will be given SAB-185, while another 421 will receive a placebo. Its primary objective is to analyse whether SAB therapy can prevent either hospitalisation or death by 28 days on enrolment. SAB Biotherapeutics co-founder, president and CEO Eddie Sullivan said: “As the Covid-19 pandemic continues to have an impact globally, we are committed to working collaboratively with our government to overcome this health crisis. “Our team is excited to be advancing SAB-185, a potent fully-human polyclonal antibody therapeutic, that offers a highly-differentiated potential treatment for patients.” NIH announced plans to fund the Phase III ACTIV-6 clinical trial to analyse various prescription and over-the-counter medications that are currently available for self-administration to treat Covid-19 symptoms.

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones. COVID-19 Survivors May Be at Increased Risk of Blood Clots One of the peculiar symptoms seen in some COVID-19 patients is blood clotting, which could lead to strokes. Studies are noting that COVID-19 survivors, especially ones with heart disease or diabetes, appear to be at increased risk of blood clots or strokes. The cause appears to be the result of prolonged immune response. The researchers, out of Nanyang Technological University in Singapore, published the results of their study in eLife. “During the initial stages of infection, SARS-CoV-2, the virus that causes COVID-19, may attack the lining of the blood vessels which can trigger inflammation and an immune response,” said Florence Chio, research assistant and first author of the study at the Lee Kong Chian School of Medicine at Nanyang Technological University. “This can result in blood vessel damage in the short term. For our study, we wanted to investigate what happens in the blood vessels of COVID-19 survivors over the longer term.” They collected blood samples from COVID-19 survivors within a month of recovery and hospital discharge. In comparison to healthy people, COVID-19 survivors have twice as many damaged blood vessel cells known as circulating endothelial cells. And they found even more damaged blood vessel cells in survivors with high blood pressure or diabetes. They also found a surplus of inflammatory proteins called cytokines that are manufactured by immune cells, in particular, an unusually high number of T-cells. “We show that an overactive immune system is the likely cause of blood vessel damage seen in some COVID-19 survivors,” Chio said. “This may cause ‘leakiness’ in the blood vessels that increases the risk of blood clots.” Processed Meat Linked to Increased Dementia Risk Researchers from the University of Leeds’ Nutritional Epidemiology Group leveraged data from 500,000 people and found that consuming 25 grams of processed meat a day is linked with a 44% increased risk of developing dementia. The study also had some confounding data, showing that eating some unprocessed red meat such as beef, pork or veal, could be protective—people who ate 50 grams a day of unprocessed meat were 19% less likely to develop dementia. The study did not specifically evaluate the impact of a vegetarian or vegan diet on dementia, although the data included people who said they did not eat red meat. Among the study group, 2,896 cases of dementia were observed over an average of eight years of follow-up. They were typically older, more economically deprived, less educated, more likely to smoke, less physically active, and more likely to have a history of stroke and family history of dementia, as well as more likely to be carriers of genes associated with dementia. Certain Hormone Drugs May Stop COVID-19 Disease Progression Investigators from the University of Pennsylvania School of Medicine conducted preclinical research suggesting that hormone drugs that decrease androgen levels might help “disarm” the SARS-CoV-2 virus’s spike protein and stop progression of severe disease. Two receptors, ACE2 and TMPRSS2, are used by SARS-CoV-2 to enter host cells, and both are regulated by the androgen hormone. In laboratory studies, they used Camostat, an androgen inhibitor, and other anti-androgen therapies and found they prevented viral entry and replication. Camostat is approved in Japan to treat pancreatitis. Other anti-androgen drugs are used to treat prostate cancer. Specific Protein Variation Might Be Key to Who is Most Affected by COVID-19 A study out of Arizona State University that evaluated MHC-I, a critical protein component of the human adaptive immune system, suggests a possible reason for why some people are severely affected by COVID-19, while others are not. Their research suggests that certain variant forms of MHC-I actually protect the body by stimulating a strong immune response, while others might leave the person susceptible to the virus. MHC-I molecules are found in all nucleated cells in vertebrates, and their primary job is helping the body clear infections from viruses and other pathogens. It does this by collecting fragments of the virus, transporting them to the cell surface and presenting them to CD8+ T-cells. MHC-I comes in a wide variety of forms, and their research suggests that certain variations do a better job of responding to the virus than others. Parkinson’s Gene May Affect How New Neurons Are Made Throughout Lifetime Scientists from the University of Sheffield and international colleagues analyzed a well-known Parkinson’s disease gene, PINK1, and discovered that not only is it linked to Parkinson’s, but it is important for generating dopamine-producing neurons through life. The research used two model systems to determine how inactivation of the PINK1 gene affects dopamine-producing neurons in adult brains. These neurons are the most severely affected brain cells in Parkinson’s. Previously, it was thought that genes linked to Parkinson’s, such as PINK1, cause early death of the neurons, and the symptoms develop when neuron numbers decrease. Now, they found that a deficiency in PINK1 caused fewer dopamine-producing neurons being made throughout life. Mutations in the PINK1 gene cause early-onset Parkinson’s, but this new finding may have consequences for future therapeutic approaches for the disease. What are Zombie Genes? Researchers at the University of Illinois at Chicago analyzed gene expression in fresh brain tissue and discovered that gene expression in certain cells increased after death. The cells not only increase their activity but grow to extremely large — “gargantuan”—proportions. They dubbed these “zombie genes,” ones that increased expression after the post-mortem interval, and discovered they were specific to a single type of cell —inflammatory cells called glial cells. They found that the glial cells grew and sprouted arm-like appendages for many hours after death. About 80% of the genes they analyzed stayed relatively stable for 24 hours, without much change in gene expression. That included so-called housekeeping genes. Another set of genes, which are present in neurons and are involved in human brain activity such as memory, thinking and seizure activity, quickly degraded in the hours after death. “That glial cells enlarge after death isn’t too surprising given that they are inflammatory and their job is to clean things up after brain injuries like oxygen deprivation or stroke,” said Jeffrey Loeb, the John S. Garvin Professor and head of neurology and rehabilitation at the UIC College of Medicine and corresponding author of the study. “Most studies assume that everything in the brain stops when the heart stops beating, but this is not so. Our findings will be needed to interpret research on human brain tissues. We just haven’t quantified these changes until now.”