Diabetes (Photo – njstatelib.org)
City of Hope and Mount Sinai scientists are the first to demonstrate that a combination treatment to regenerate beta cells can increase human insulin-producing cells In Vivo.
By News Desk
In preclinical studies, a team of researchers from City of Hope in Duarte and Mount Sinai Health System in New York reports new findings on a therapeutic combination that regenerated human insulin-producing beta cells, providing a possible new treatment for diabetes. The findings were published on July 10 in Science Translational Medicine.
This work, led by Andrew F. Stewart, M.D., Irene and Dr. Arthur M. Fishberg Professor of Medicine and Director of the Mount Sinai Diabetes, Obesity and Metabolism Institute, began at the Icahn School of Medicine at Mount Sinai in 2015. The studies were a team effort. Adolfo Garcia-Ocaña, Ph.D., formerly a professor at Mount Sinai who is now at City of Hope, and his research team designed the studies and performed the novel, extensive and detailed animal transplant and drug treatment models using beta cells from donors. Final studies took place at City of Hope in 2023.
For the study, the natural product harmine, which is found in some plants, was combined with a widely used class of type 2 diabetes therapy called GLP1 receptor agonists. Researchers transplanted a small number of human beta cells into mice that had no immune system and that also served as a standard model of type 1 and type 2 diabetes; these mice were treated with the combination therapy and their diabetes was rapidly reversed. Strikingly, human beta cell numbers increased by 700% over three months with this drug combination.
“This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo. This research brings hope for the use of future regenerative therapies to treat the hundreds of millions of people with diabetes,” said Dr. Garcia-Ocaña, the paper’s corresponding author.
“It has been remarkable to watch this story unfold over the past 15 years,” said Dr. Stewart, who, along with Peng Wang, Ph.D., professor of Medicine (Endocrinology, Diabetes and Bone Disease) at Icahn 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. “The steady progression from the most basic human beta cell biology, through robotic drug screening and now moving to human studies, illustrates the essential role for physician-scientists in academia and pharma.”
Growing new beta cells
More than 10% of the world’s adult population has diabetes, a disease defined by high blood sugar levels. In both type 1 and type 2 diabetes, a reduction in both the quantity and quality of insulin-producing beta cells causes high blood sugar. Unfortunately, none of the commonly used diabetes therapies are able to increase human beta cell numbers, and therefore cannot completely reverse diabetes.
Fortunately, most people with diabetes have some residual beta cells, which is what inspired the research team to search for ways to restore their numbers.
“Our studies pave the way for moving DYRK1A inhibitors into human clinical trials, and it’s very exciting to be close to seeing this novel treatment used in patients,” Dr. Garcia-Ocaña said. “There is nothing like this available to patients right now.”
Other critical members of the team include Mount Sinai’s Carolina Rosselot, Ph.D., Yansui Li, Ph.D., and Alexandra Alvarsson, Ph.D. Additional City of Hope authors on the paper are Geming Lu, M.D., assistant research professor, and Randy Kang, senior research associate, who are both members of Dr. Garcia-Ocaña’s lab.
Drs. Stewart and DeVita are named co-inventors on patent applications for DYRK1A inhibitors, such as harmine, for the treatment of diabetes. These patent applications are filed through the Icahn School of Medicine at Mount Sinai and are currently unlicensed.
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