Another Repurposing of an Old Drug: Pargyline to Protect Beta Cells in Type 1 Diabetes

Protecting Beta Cells Against Stress May Guard Against Type 1 Diabetes:

An existing drug boosts survival for insulin-producing cells under autoimmune attack.

BOSTON – (July 27, 2020) – Type 1 diabetes occurs when a person’s own immune system destroys insulin-producing beta cells in the pancreas. In recent years, scientists have learned how to grow large volumes of replacement beta cells, but the researchers are still trying out many options to protect these cells against the immune attack. Joslin Diabetes Center researchers now have found an unusual strategy that eventually may help to guard such transplanted beta cells or to slow the original onset of the disease.

Research in mouse models and in human cells has shown that targeting a protein called renalase may protect beta cells against autoimmune attack by strengthening them against stress, says Stephan Kissler, an investigator in Joslin’s Section on Immunobiology, associate professor of medicine at Harvard Medical School, and co-senior author on a paper describing the work in Nature Metabolism.

Kissler, co-senior author Peng Yi, PhD, and their colleagues also demonstrated that an existing FDA-approved drug inhibits renalase and increases the survival of beta cells in those lab models.

The Joslin study joins a growing set of evidence suggesting that functional problems with beta cells themselves may help to trigger the autoimmune attack in type 1 diabetes, say Kissler and Yi, who is an assistant investigator in the Islet Cell and Regenerative Biology Section. “You might have genes that make the beta cell a little bit dysfunctional and more prone to becoming a target of the immune system,” Kissler explains.

The research began with a casual hallway conversation between Kissler and Yi about potential ways to protect beta cells from autoimmune attack. The two ended up launching a bold gamble to try inhibiting genes across the genome, one at a time, using a screening technique based on the CRISPR gene-editing method with a beta cell line from a “non-obese diabetic” (NOD) mouse that models type 1 diabetes. “Whole genome CRISPR screening is a powerful tool for new target discovery and we hoped that it would help us find any mutations that protect the beta cell,” Yi says.

Moar: https://www.joslin.org/about/news-media/protecting-beta-cells-against-stress-may-guard-against-type-1-diabetes