Drug Duo Speeds Regeneration of Key Cells Lost in Diabetes
A novel combination of two drugs appeared to spur faster regeneration of insulin-producing beta cells in the pancreas, a preliminary study in mice and human tissue found.
Beta cells are crucial to making insulin, a hormone that's deficient in people with type 1 and type 2 diabetes.
The new drug combo pairs an already approved class of type 2 diabetes medications called GLP-1 receptor agonists with an experimental drug called harmine.
"In the United States, 30 million people have diabetes. As many as 80 million have prediabetes. Worldwide, there are 400 million people with diabetes. All of those people have inadequate numbers of beta cells," explained senior study author Dr. Andrew Stewart. He's director of the Mount Sinai Diabetes, Obesity and Metabolism Institute in New York City.
Stewart and his team have been working on developing drugs that will make beta cells regenerate. The hope is that if enough beta cells can be created, people won't need any additional diabetes treatment.
In 2015, the researchers found that harmine could coax the beta cells into regenerating. But only about 2% of cells regenerated in a day. "In someone with type 1 diabetes, they've lost about 90% of their beta cells. Two percent a day isn't fast enough," Stewart explained.
The team found another drug that boosted beta cell regeneration, but that drug might have caused significant side effects.
One graduate student and member of Stewart's team from Mount Sinai's Icahn School of Medicine, Courtney Ackeifi, looked at a number of potential drugs to combine with harmine, with the hope of boosting its beta cell regeneration power. A popular class of medications used to treat type 2 diabetes, GLP-1 receptor agonists (Trulicity, Ozempic, Victoza and others), turned out to offer a potent combination when added to harmine.
"If you combine harmine with any member of the GLP-1s, which are used in millions of people with diabetes, they're converted into beta cell-regenerating drugs that replicate at a rate of 5 to 8% a day," Stewart said.
The study showed that the researchers were able to get normal human beta cells and beta cells from people with type 2 diabetes to regenerate.
The researchers also transplanted human beta cells into mice. When those mice were given the drug combination, the beta cells regenerated. There were no serious short-term side effects in the weeklong treatment.
But whenever medications can prompt cells to replicate, there's always a concern that other cells might also regenerate -- and that's not always a good thing. Stewart said the research team has received a grant from JDRF to study the long-term safety of this drug combination.
The researchers also don't know how long the beneficial effects of the drug combination will last -- and if the effects wear off, how often the treatment might need to be given.
Another issue to be addressed is for people with type 1 diabetes. The autoimmune attack that destroys beta cells and causes type 1 diabetes in the first place may still be ongoing. That means it's possible that any new beta cells created could be destroyed. Research into suppressing this autoimmune attack is ongoing.
One expert not involved with the study called it a novel approach, but had questions.
"This is a very interesting finding," said Matthias Hebrok, director of the University of California, San Francisco Diabetes Center. "The advance is in seeing that a combination of drugs -- one of which is being used in people with diabetes already -- overrides the internal blocks that exist in beta cells to prevent them from proliferating."
Hebrok said as with any study, there are many questions still to be answered. The biggest concern is that the researchers may be "trying to proliferate cells that might be compromised," he said.
"For someone to get type 2 diabetes, beta cells don't function as they should. Most people who are obese don't get diabetes. Their beta cells can keep up with the demand. In type 2, the beta cells are inadequate. Even if you make more, it might not work because you've just increased inadequate cells," Hebrok explained.
Stewart said he is hopeful. "We've gone from thinking this was impossible and undoable just five years ago to showing that substantial increases in the rates of beta cell regeneration are possible. Things are moving at a rate that is unprecedented," he said.
The study was published Feb. 12 in the journal Science Translational Medicine.
In this video supplied by Mount Sinai, researchers explained their findings:
Learn more about beta cells from Diabetes.co.uk.
SOURCES: Andrew Stewart, M.D., director, Mount Sinai Diabetes, Obesity and Metabolism Institute, New York City; Matthias Hebrok, Ph.D., director, UCSF Diabetes Center, San Francisco; Feb. 12, 2020, Science Translational Medicine