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    February 7, 2023

    Drug Discovery Industry Roundup with Barry Bunin — February 7, 2023

    Barry Bunin, PhD Founder & CEO Collaborative Drug Discovery Barry Bunin, PhD
    Founder & CEO
    Collaborative Drug Discovery

    Drug Discovery Industry Roundup with Barry Bunin

    "Martyr Microbes Protect the Pack by Sensing a Viral Attack." That headline in a recent Drug Discovery News article certainly catches one's attention. It begins: "Bacteria and the bacteriophages that infect them engage in a never-ending evolutionary battle. 'Because of this constant warfare, each side has evolved elaborate mechanisms to out the other one'…"  I thought it was interesting given all the excitement around CRISPR Cas9 as a prokaryotic immune response for bacteria to viral infections. This new story describes the work of Michael Laub, an immunologist at the Massachusetts Institute of Technology, who recently published a paper in Nature about a phage protein called the major capsid that induces an abortive infection system, or programmed suicide, by interacting with a bacterial protein called CapRel. Cell suicide is believed to be a defense mechanism to ensure that phages won't continue to propagate, infecting other cells. The article quotes Joseph van Belleghem, an immunologist formerly at the University of Zurich who was not involved in the study, on the value of the research for phage therapies, in which phages fight bacterial infections in humans. Belleghem says: "If we can decipher which type of bacteria and which type of phages elicit a certain type of resistance mechanism, we can make educated guesses on which phages to use."  And from Joseph Bondy-Denomy, a microbiologist and immunologist from UCSF who was also not involved in the study: "This is the start of an explosion of antiviral systems that detect structural proteins. There are so many of these systems that are based on small molecule signals. I feel like it's going to lead to new drugs."   

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    "Obesity Drugs Are Pharma's Hot New Trend." That headline from Bloomberg summarizes what they see as renewed interest in providing medications to battle obesity-in a bit of an arms race triggered, at least in part, by Novo Nordisk, the maker of the Wegovy injection that mimics the weight-related hormone GLP-1. This is a drug we've been following closely in PharmaKB "The Pharmaceutical KnoweldgeBase" which we recently launched at www.pharmaKB.com. Because of the excitement over Lilly's drug Moujaro (tirzepatide) which also hits GLP-1 and a second target as mentioned in a recent FDA announcement I checked it out in PharmaKB, curious to see the top terms showing up in the literature for this new drug, based on the daily feed from PubMed Central. This finds some patients anecdotally saying they just weren't hungry anymore-and thus would not mind if they kept taking the drug for life. And the first-time new MESH terms appeared in the literature together with the drug. Both drugs seem to help people lose weight, with Mounjaro showing a remarkable 21-22.5% weight loss at the highest dosage. Because PharmaKB has the disease information (MESH and ATC), I was able to quickly find the other drugs hitting the same target (Glucagon-like peptide-q (GLP-1) analogues) in a single click to the WHO. Going back to the Bloomberg article, it reads: "For a long time, obesity drug development was out of favor as Big Pharma focused on other lucrative arenas such as cancer. Now obesity medicines are making a roaring comeback, thanks to a new class of diabetes drugs that also turn out to be surprisingly potent weight loss agents. The new drugs mimic the effects of natural hormones called incretins that are secreted from the gastrointestinal tract and tell the body food has been eaten." The article provides an overview of the different approaches pharmaceutical researchers are taking, and also notes a non-scientific challenge they all will face: "The biggest question mark of all is whether drugmakers can convince insurance companies to cover the new medicines. Spotty coverage has been a long-standing problem for obesity drugs."

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    A Therapeutic Intervention for Aging? Now that's something that should attract quite a market. Derek Lowe, in his always-fascinating blog in Science, writes about the role of retroviruses in cellular aging. Lowe notes that it's already known that endogenous retrovirus sequences have influenced the evolution of the human immune system and can be involved in some forms of cancer. He then points to a new paper, that looks at their role in aging and identifies a new culprit, HERV-K. The paper shows that HERV-K envelope proteins (and their associated mRNAs) are detectable at greater and greater levels as cells age, and that this relationship holds in rodents and primates (by cell, tissue, and serum assays), and even in tissue and serum from aged human donors. Lowe notes that because HERV-K is associated with cellular senescence, "This effect could be reversed by treatment with an anti-HERVK-envelope-protein antibody. … This presents an opportunity for therapeutic intervention." Lowe ends his blog with a sense of excitement: "It's certainly possible that the underlying aging phenotype is being exacerbated, perhaps greatly, by this route, and that we could alleviate things by targeting it. Let's find out!"  It is an interesting POC that one can effect aging, albeit in an artificially constructed system, but still interesting.

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    Could Serine Supplements Help Protect Against Diabetic Neuropathy? That's the question raised by a paper from the Salk Institute, recently published in Nature, that showed that low levels of the amino acid serine put diabetic mice at risk for developing peripheral neuropathy. An article in FIERCE Biotech reports the scientists are using their findings to develop a test that can indicate whether a patient could benefit from serine supplementation, which alleviated neuropathy symptoms in mice with diabetes. The article notes that of the 37 million patients in the U.S. with Type 2 diabetes, about half of them suffer from peripheral neuropathy, according to National Institutes of Health estimates. The condition causes numbness, pain and weakness in the hands and feet. Treatments exist, but they aren't particularly effective. Serine is a building block of sphingolipids, fat molecules found heavily in the nervous system that are thought to be involved in tissue development, cell adhesion and more. The article explains that while it's tempting to jump to trying serine supplementation in humans with neuropathy, the reality is more complicated. The researchers noted that people would likely need to take high doses of it to make a difference, and not everyone needs more, which is why they plan to develop a serine tolerance test akin to the oral glucose tolerance test that's used to diagnose diabetes. This will help clinicians understand which patients might perhaps benefit from serine supplements.

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    Barry A. Bunin, PhD, is the Founder & CEO of Collaborative Drug Discovery, which provides a modern approach to drug discovery research informatics trusted globally by thousands of leading researchers. The CDD Vault is a hosted biological and chemical database that securely manages your private and external data.

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