A new drug combination has shown the ability to boost insulin-producing cells by an astonishing 700% in mice. This remarkable discovery could potentially revolutionize the treatment of diabetes.
With over 537 million adults worldwide living with diabetes and projections suggesting this number could rise to 783 million by 2045,1 the need for innovative therapies is more pressing than ever.
As research progresses, this breakthrough offers renewed hope for millions of individuals struggling with diabetes.
A Novel Approach to Treating Diabetes
The research, led by Andrew Stewart of the Icahn School of Medicine at Mount Sinai in New York and City of Hope in Los Angeles, began in 2015 and culminated in the publication of their findings in Science Translational Medicine.
The team’s innovative work involved administering a combination of harmine, found in certain plants, and GLP1 receptor agonists, a type 2 diabetes treatment, to mice lacking an immune system and serving as models for both type 1 and type 2 diabetes.(ref)
Over the course of three months, the researchers observed a remarkable 700% increase in human beta cell numbers in the treated mice. This achievement marks the first instance of a drug treatment proven to amplify adult human beta cell quantities in vivo, offering a potential regenerative therapy for the vast number of individuals affected by diabetes.
Challenges Posed by Diabetes & Current Therapies
Diabetes affects over 10% of the global adult population, with a decrease in both the number and quality of insulin-producing beta cells characterizing the condition. Current therapies fall short in adequately increasing human beta cell numbers to reverse diabetes, necessitating innovative solutions.
The research team sought methods to replenish the residual beta cells present in most diabetic individuals, leveraging advanced laser microscopy techniques to accurately gauge the mass of human beta cells in islet grafts. This meticulous assessment revealed a significant increase in beta cell mass through enhanced proliferation, function, and survival of human beta cells.
Harnessing the Power of Harmine & GLP1 Receptor Agonists
Harmine, a natural compound found in certain plants, has been identified as a small-molecule inhibitor of dual-specificity tyrosine-regulated kinase 1A (DYRK1A), which plays a crucial role in beta cell replication.
When combined with GLP1 receptor agonists, a class of diabetes drugs that includes exenatide, liraglutide, lixisenatide, and semaglutide, harmine exhibits a synergistic effect on human beta cell proliferation.(ref)
This synergy was observed in both in vitro studies using human pancreatic islets from cadaveric donors and in vivo experiments involving euglycemic and immunodeficient diabetic mice. The combination therapy not only increased beta cell replication but also normalized glucose levels in diabetic mice, outperforming either drug alone or saline.
Safety & Tolerability of Harmine
To explore the safety and tolerability of harmine in humans, the Mount Sinai team received approval from the U.S. Food and Drug Administration in 2021 to conduct a phase 1 study in healthy volunteers. Although harmine is a monoamine oxidase inhibitor (MAOI), no psychoactive properties have been identified in animal studies at the doses employed by the researchers.
The phase 1 study, led by James Murrough, MD, PhD, aims to determine the maximum tolerable dose of harmine in humans and assess any potential undesirable central nervous system, cardiovascular, or other effects. This crucial step will provide valuable insights into the safety profile of harmine before proceeding to further clinical trials.
Future Directions & Clinical Applications
Looking ahead, the team aims to translate these findings into clinical applications by conducting phase 1 trials to evaluate the safety and tolerability of harmine in healthy volunteers. The development of next-generation DYRK1A inhibitors by Robert J. DeVita, PhD, paves the way for further human studies to assess potential toxicity risks and determine dosing for clinical trials.(ref)
Researchers also plan to explore inducers of beta cell regeneration in conjunction with immunomodulators to counteract the immune system’s attack on newly formed beta cells in patients with type 1 diabetes. This multifaceted approach aims to create an environment conducive to the growth and maintenance of new beta cells, ultimately enhancing insulin levels and ameliorating the condition.
The collaborative efforts of researchers from different institutions, funded by various organizations, including the National Institutes of Health (NIH) and BreakthroughT1D, underscore the dedication to finding innovative solutions for diabetes.
As the research progresses, it offers renewed hope to millions of individuals grappling with this widespread condition, potentially revolutionizing diabetes management in the near future.
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Martha A. Lavallie
Martha is a journalist with close to a decade of experience in uncovering and reporting on the most compelling stories of our time. Passionate about staying ahead of the curve, she specializes in shedding light on trending topics and captivating global narratives. Her insightful articles have garnered acclaim, making her a trusted voice in today's dynamic media landscape.
