Scientists demonstrate a combination treatment can increase human insulin-producing cells in vivo

Key Takeaways

• Researchers have developed a combination therapy that increased numbers of insulin-producing beta cells in a mouse model.
• According to the researchers, this is the first time scientists have developed a drug treatment that increased adult human beta cell numbers in an animal.

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 many commonly used diabetes therapies can increase human beta cell numbers, and therefore cannot completely reverse diabetes.

In Science Translational Medicine, a team of researchers from Mount Sinai Health System in New York City and City of Hope in Los Angeles report new findings on a therapeutic combination that regenerated human insulin-producing beta cells, providing a possible new treatment for diabetes. 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. The researchers transplanted a small number of human beta cells into mice that have no immune system and that also serve 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 [in an animal]. This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes,” said Dr. Garcia-Ocaña, the paper’s corresponding author.

The Mount Sinai team recently completed a Phase I clinical trial of harmine, which inhibits an enzyme in beta cells called DYRK1A, in healthy volunteers to test its safety and tolerability. They have also developed next-generation DYRK1A inhibitors. Mount Sinai is conducting studies to test these in humans for potential toxicity risks and estimate dosing for clinical trials and is planning to initiate first-in-human trials with independent research teams next year.

The researchers also want to address the fact that in patients with type 1 diabetes, the immune system will continue to kill new beta cells. Therefore, the team plans to test inducers of beta cell regeneration together with immunomodulators that regulate the immune system. Their goal is for the combination to allow new beta cells to thrive and improve insulin levels.

Edited by Miriam Kaplan, PhD

Source:

The Mount Sinai Hospital, Medical Xpress, July 10, 2024; see source article