One Step Closer to a Cure: Breakthrough “Harmine Pill” Sparks Hope for 500 Million Diabetics Worldwide

Mount Sinai researchers discovered that harmine, a beta cell regenerative drug, may transform alpha cells into beta cells, offering scalable diabetes treatment options for millions.

Researchers and bioinformaticians at the Icahn School of Medicine at Mount Sinai have unveiled new insights into the mechanisms behind human beta cell regenerative drugs, offering a potential breakthrough for the over 500 million people worldwide living with diabetes. These findings, recently published in Cell Reports Medicine, could mark a significant step forward in diabetes treatment.

Diabetes occurs when pancreatic beta cells lose their ability to produce insulin, a hormone critical for maintaining healthy blood sugar levels. Despite significant advancements, there are still no widely scalable therapeutic solutions capable of addressing the global diabetes crisis.

For over 15 years, scientists at Mount Sinai have been dedicated to finding a cure by developing drugs that stimulate the regeneration of human beta cells, bringing renewed hope to millions of patients worldwide.

Discovery of Harmine and Its Enhancements

In 2015, Mount Sinai researchers discovered the first such drug, called harmine. Harmine is a member of a class of drugs called DYRK1A inhibitors. In 2019 and 2020, the researchers reported that DYRK1A inhibitors can synergize with TGF-beta signaling as well as GLP-1 receptor agonist (GLP-1RA) drugs such as semaglutide (e.g., Ozempic) and exenatide (Byetta) to induce more robust levels of human beta cell regeneration. Finally, in July 2024, they showed that harmine alone increases human beta cell mass by 300 percent, and if a GLP-1RA is added, by 700 percent.

A key question has been how harmine causes beta cells to regenerate. In the newest study, the research team reports that the new, regenerated beta cells may be coming from an unexpected source: a second pancreatic cell type called alpha cells. Since alpha cells are abundant in people with type 1 and type 2 diabetes, they may be able to serve as a source for new beta cells in both common types of diabetes.

“This is an exciting finding that shows harmine-family drugs may be able to induce lineage conversion in human pancreatic islets,” says Esra Karakose, PhD, Assistant Professor of Medicine (Endocrinology, Diabetes and Bone Disease) at the Icahn School of Medicine at Mount Sinai and corresponding author of the study. “It may mean that people with all forms of diabetes have a large potential ‘reservoir’ for future beta cells, just waiting to be activated by drugs like harmine.”

A Decade-Long Collaborative Effort

“It has been remarkable and rewarding to watch this multi-group story unfold over the past 15 years,” added Andrew F. Stewart, MD, Irene and Dr. Arthur M. Fishberg Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Director of the Mount Sinai Diabetes, Obesity, and Metabolism Institute. He and Peng Wang, PhD, Professor of Medicine (Endocrinology, Diabetes, and Bone Disease) at the Icahn School of Medicine at Mount Sinai, conceived of and performed the initial high-throughput drug screen that led to the discovery of harmine, described in Nature Medicine in 2015.

“A simple pill, perhaps together with a GLP1RA like semaglutide, is affordable and scalable to the millions of people with diabetes,” said Dr. Stewart.

Reference: “Cycling alpha cells in regenerative drug-treated human pancreatic islets may serve as key beta cell progenitors” by Esra Karakose, Xuedi Wang, Peng Wang, Saul Carcamo, Deniz Demircioglu, Luca Lambertini, Olivia Wood, Randy Kang, Geming Lu, Donald K. Scott, Adolfo Garcia-Ocaña, Carmen Argmann, Robert P. Sebra, Dan Hasson and Andrew F. Stewart, 2 December 2024, Cell Reports Medicine.
DOI: 10.1016/j.xcrm.2024.101832

The work represents a combined effort by the Icahn School of School of Medicine at Mount Sinai team: Dan Hasson, PhD, Associate Professor of Oncological Sciences, and Dermatology, and Director of the Bioinformatics and Next-Generation Sequencing (BiNGS) Core; Robert Sebra, PhD, Professor of Genetics and Genomic Sciences, Director of the Center for Advanced Genomic Technology, and Director of Technology Development for the Genomics Core Facility; Robert J. DeVita, PhD, Professor of Pharmacological Sciences and Director of the Medicinal Chemistry Core of the Drug Discovery Institute; and long-term collaborator Adolfo Garcia-Ocana, PhD, formerly a professor at the Icahn School who is now the Ruth B. and Robert K. Lanman Chair in Gene Regulation and Drug Discovery Research and chair of the Department of Molecular and Cellular Endocrinology at City of Hope. The Mount Sinai team is moving these studies to human trials.

The work has been supported for decades with funding from the National Institutes of Health, the National Institute of Diabetes Digestive and Kidney Disease, By BreakthroughT1D, formerly JDRF, as well as through additional generous philanthropic gifts.

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