New Drug Combination Achieves Highest Rate of Human Beta Cell Proliferation

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In 2015, JDRF-funded researchers, including Andrew F. Stewart, M.D., of the Icahn School of Medicine at Mount Sinai, discovered the first drug—harmine—that is able to make human beta cells proliferate. This was a major advance, but the rates of regeneration—2 percent—were lower than needed to rapidly expand beta cells in people with diabetes. Now, they report in Cell Metabolism that a new cocktail of drugs, which combines harmine with a class of drugs called “TGF-beta inhibitors,” was able to produce rapid rates of human beta cell expansion, averaging 5 percent to 8 percent per day (with occasional proliferation rates as high as 15 percent to 18 percent!).

This new drug combination now faces another hurdle: Harmine and TGF-beta inhibitors both have adverse effects on cells other than beta cells, so methods for delivering it exclusively to beta cells in humans, and not to other cells, must still be developed. But, if successful, it will be a major step toward a cure for T1D.

Dr. Stewart was not a diabetes investigator when he first came into research more than 40 years ago. He was focused on osteoporosis, a condition where the body’s bones become weak and brittle. The substance that Dr. Stewart worked on (called PTHrP), also drove beta cell replication, survival and expansion.

“I am an endocrinologist, taking care of people with diabetes, and so it didn’t take long to appreciate that there might be promise here for human beta cell regeneration,” says Dr. Stewart. “I applied for my first JDRF grant in the late 1990s—despite having no prior ties to diabetes research and being an outsider in the diabetes world of scientists—and JDRF embraced me immediately.”

He added, “This is the latest advance in a long string of beta cell advances and surprises, continuously supported and encouraged by JDRF.”

He has now worked on diabetes research for almost 20 years.

Hear how JDRF is working to cure type 1 diabetes through its beta cell regeneration program here.