October 4, 2023
Barry Bunin, PhD Founder & CEO
Collaborative Drug Discovery
A Well-Deserved Nobel Prize for Two mRNA Pioneers. The New York Times coverage of the Nobel Prize in Physiology or Medicine being awarded to Katalin Karikó and Drew Weissman, who together identified a chemical tweak to messenger RNA, was a reminder about the value of basic research. It should also be a nudge to increase the support of basic medical research, which of course directly paid off with the COVID vaccines. The story details the years in which Karikó and Weissman toiled in obscurity, and the paucity of grant money as they discovered a way to create mRNA that wasn’t seen as an invader, but accepted into cells—opening the gates for a new approach to creating vaccines. The article includes this nugget: “Dr. Karikó said that every October, her mother used to tell her, ‘I will listen to the radio that maybe you will get the Nobel Prize.’ Dr. Karikó said she would answer: ‘Mum, you know, I never even get a grant.’” In a PNAS interview, Dr. Karikó shares the steps from her joining BioNTech to the moment that impacted so many peoples’ lives:
"In 2013, I left Philadelphia to join BioNTech, where I continued to improve the mRNA and its formulation. Two years later, our CEO Uğur Şahin, a visionary scientist, announced that the company had a moral obligation to begin vaccine development against infectious pathogens. Later, in 2018, we partnered with Pfizer to develop mRNA vaccines, specifically against the influenza virus. By the end of 2019, we were poised to begin clinical trials, when the coronavirus pandemic struck. In January 2020, Uğur realized that we had to pivot to developing a vaccine for SARS-CoV-2, given the news from Wuhan, China. He designed the coding sequence for the mRNA vaccine based on the information coming from Wuhan.”
For the full interview, see: https://www.pnas.org/doi/10.1073/pnas.2119757118.
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Biotech to the Rescue. From that same New York Times article, above, biotech can take pride in their ability to identify genius being ignored elsewhere. The article recounts how unable to get a grant while at the University of Pennsylvania, Dr. Karikó said she was told she was “not faculty quality” and was forced to retire from the university a decade ago. She remains only an adjunct professor there. When Karikó and Weissman were ready to release their work on how making the changes to mRNA synthesized in the lab before injecting it into cells allowed it to be taken up by cells without provoking an immune response, few journals were interested. “Their paper, published in 2005, was rejected by the journals Nature and Science,” Dr. Weissman said. The study was eventually accepted by a niche publication called Immunity. But two biotech companies soon took notice: Moderna, in the United States, and BioNTech, in Germany, where Dr. Karikó eventually became a senior vice president.” The Washington Post carries more about the long struggle of Karikó and Weissman in an article headlined “Years of Research Laid the Groundwork for Speedy COVID-19 Shots.”
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"The World Needs New Antibiotics. The Problem Is, No One Can Make Them Profitably”. That’s the headline from a Wall Street Journal article looking at the bleak financial picture many pharmaceutical companies face when developing much needed antibiotics. The article reads, in part, “The push for antibiotics to fight fast-evolving superbugs is snagging on a broken business model. Six startups have won Food and Drug Administration approval for new antibiotics since 2017. All have filed for bankruptcy, been acquired or are shutting down. About 80% of the 300 scientists who worked at the companies have abandoned antibiotic development,” according to Kevin Outterson, executive director of CARB-X, a government-funded group promoting research in the field.” Part of the problem is that new antibiotics are intended to be used only infrequently—when all else fails—to guard against resistant strains of bacteria developing. Infrequent use translates into infrequent sales, which translates into the need for higher prices be when hospitals and patients are used to spending much less for antibiotics. Some have suggested that new antibiotics get the same type of support the U.S. government provides to developers of treatments for rare diseases under the Orphan Drug Act of 1983.
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A “Prozac Moment” for Ozempic?” The Economist carries an article suggesting that semaglutides such as Ozempic and Wegovy could revolutionize the treatment of alcoholism in the same way that the introduction of Prozac (which had fewer side effects than other antidepressants being used at the time) made it easier for physicians to prescribe medication for those suffering from depression. The article notes that “Nearly 30 million Americans suffer from alcohol-use disorder, meaning that alcohol has a significant and negative impact on their lives. Over 140,000 die from alcohol-related causes each year: alcohol is the fourth-highest cause of preventable death in America.” It points to the fact that Disulfiram, also known as Antabuse, was approved by the FDA in 1951; Naltrexone was approved in 1984, and acamprosate 20 years later. They help reduce alcohol cravings and make withdrawal more manageable—but remain little used. With patients reporting reduced alcohol cravings while on Ozempic and Wegovy, and animal trials producing similar findings, some feel that semaglutides could play a role in getting more people to try this intervention. Kyle Simmons, Professor of Pharmacology at Oklahoma State University, says: “This drug could be a Prozac moment for addiction medication.”
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Beyond the “Hemp for Everything Cult” an Interesting Paper on CBD and Inflammation. Derek Lowe, in his recent blog for Science, points to a new paper on the potential for CBD to be used for inflammation. He begins with something of a disclaimer, noting “I will also freely admit to being irritated by the hemp-for-everything cult that regards the plant as a biological miracle that’s good for anything that ails you.” He then points to the paper and says “There have been reports that CBD can have real cellular effects, in particular inhibition of reactive oxygen species formation, effects on the levels of TNF-alpha, and on cytokine release in general. But the mechanisms behind these have not been very clear. The authors show here, though, that cannabidiol has several effects on lipid mediator production from fatty acids. Specifically, it seems to suppress leukotriene production via 5-lipoxygenase while setting off greater activity in the 15 lipoxygenase (and 12-lipoxygenase) pathways. In fact, it looks like CBD might be an allosteric activator of 15-lipoxygenase-1. The authors show effects consistent with these explanations both in cell assays and in a mouse model of inflammation.” In summary, Lowe writes: “So there are some parts that need to be filled in. But the overall story of shifting from pro-inflammatory to inflammation-resolving pathways is well worth the effort—and it’s also worth seeing if there are even better molecules than CBD that might have these effects.”
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.