August 30, 2023
Barry Bunin, PhD Founder & CEO
Collaborative Drug Discovery
“Health Officials Warn of New, Highly Mutated COVID Strain BA.2.86.” This headline from The Seattle Times is a reminder that COVID is still with us, mutating away to send new challenges our way. BA.2.86 appears to descend from the BA.2 variant that emerged in early 2022, but the new lineage has more than 30 mutations on its spike protein, according to Ryan Hisner, an independent researcher who has closely tracked COVID’s evolution. The article quotes Kristian Andersen, a Scripps Research immunologist and microbiologist, as saying: BA.2.86’s mutations give it “all the hallmark features of something that could take off.” Fortune reports that the World Health Organization and the U.S. Centers for Disease Control and Prevention are tracking BA.2.86—formerly referred to as BA.X and dubbed “Pirola” by variant trackers. “What sets this one apart from the many other Omicron subvariants is that it exhibits a large number of mutations … far more than we usually see,” Ryan Gregory, a biology professor at the University of Guelph in Ontario, told Fortune. While only six sequences—and counting—of the variant had been identified in four countries (Denmark, England, the U.S., and Israel) as of late Friday, sequencing worldwide is at an all-time low. Meanwhile, CNBC reports Moderna says its new COVID vaccine is effective against the now-dominant Eris variant in early trials.
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“Ozempic Settles the Obesity Debate: It’s Biology Over Willpower.” That’s the headline from a Wall Street Journal article on how new weight-loss drugs affect the brain in ways that help researchers understand how the body regulates weight. The article reads, in part: “Ozempic and similar drugs are transforming the world’s understanding of obesity. It isn’t so much about willpower: It’s about biology. The success of the powerful new class of diabetes and weight-loss drugs shows how important chemistry is to determining a person’s weight. The brain is the body’s chief chemist, regulating appetite and making it difficult for many people to shed pounds and keep them off. The brain determines how much fat it wants people to carry, according to years of research bolstered by the new drugs.”
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The Road to Ozempic and Wegovy Included Empty Auditoriums and Gila Monsters. That’s just part of a fascinating historical look at the research that has produced the widely popular weight-loss drugs as reported in The New York Times. The story traces the path back to the early 1980s when a discoverer of GLP-1 found himself from the late 1980s to the early 1990s scheduled late on the last day of Endocrine Society meetings, speaking to nearly empty auditoriums. “Everyone had left for the airport — people were taking down the exhibits,” said Dr. Daniel Drucker, who studies diabetes and obesity at the Lunenfeld-Tanenbaum Research Institute in Toronto and who consults for Novo Nordisk and other companies. “It was a pretty lonely field.” The article, with its historic perspective, provides a valuable look into the drug discovery process, and shows the benefit of scientific curiosity—including that of Bronx VA researcher John Eng, who in 1990 was looking for interesting new hormones that might be useful medications. He was intrigued by the fact that the venomous Gila monster somehow kept its blood sugar levels stable when it did not have much to eat. This led to his discovery of an interesting chemical in the lizard’s saliva: a variant of GLP-1.
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“The Aging Brain: Is Misplaced DNA to Blame?” That’s the question that Derek Lowe explores in his recent blog for Science. I enjoy how he plays points, off counterpoints—for example regarding aging, he writes: “Thermodynamically you can blame entropy, creeping disorder spreading through the system, and that really does seem to be what happens (see below). But living systems are not thermodynamically closed—we can in theory put energy into them and repair things, the same way that you can clean your kitchen when things start to pile up in the sink and on the counters. In theory.” He points to a new paper on the cGAS-STING pathway which is constantly checking for the presence of double-stranded DNA out in the cytosol, where it shouldn’t be. “That would normally be the sign of a viral infection (viral DNA floating around), and that’s how the body reacts to it (that STING name is short for ‘stimulator of interferon genes’). There are autoimmune diseases such as lupus where dsDNA gets spread around to the point that it sets off this inflammatory pathway. A lot of cGAS-STING research comes from that direction, and since immunotherapy is such a huge field in cancer treatment these days, this mechanism gets a lot of attention there, too. Well, another condition that is characterized by a constant inflammatory response (apparently in the absence of infection as well) is. . .aging. It’s a clear source of trouble in a number of different tissues—this has been recognized for some time now, and a great deal of work has gone into figuring out why this happens and what might be done about it. Several years ago it was recognized that the cGAS- STING system was a key part of the inflammation seen in microglial cells in the aging brain (and in the brains of people with neurodegenerative diseases).” While noting potential problems of dialing down cGAS-STING perhaps also dialing down the response to viral infections, he sees plenty of reasons to go forward with research in the area. He concludes: “It may be that just in the same way that there appear to be tradeoffs between aging and cancer, there may be others between aging and the ability to deal with viruses. But let’s find out!”
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“Erasing Epigenetic ‘Memory’ to Improve the Quality of Stem Cells.” Researchers may find hope in this recent headline from FIERCE Biotech. The article notes it’s been 16 years since scientists first coaxed skin cells back into their embryonic state, a development that made it possible to sidestep the thorny ethical dilemmas around sourcing human stem cells from fetal tissue to produce them en masse. Progress in regenerative medicine has been hampered by the fact that while the resulting induced pluripotent stem cells, or iPS cells, are very similar to natural stem cells, their genomes still carry the biological “memories” of the cells from which they were derived. The article points to a study recently published in Nature by a research team led by scientists from Australia’s Harry Perkins Institute of Medical Research, the University of Western Australia, Monash University and the University of Adelaide that describes how they developed a method that resets a cells’ genes so they look just as they did in the earliest stages of embryonic development. The article quotes study co-lead Jose Polo, Ph.D., an epigeneticist at Monash as saying: “This significantly reduces the differences between iPS cells and [embryonic stem cells] and maximizes the effectiveness of how human iPS cells can be applied.”
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. CDD Vault® is a hosted biological and chemical database that securely manages your private and external data.