Inhibition of polyamine biosynthesis preserves β cell function in type 1 diabetes

Type 1 diabetes is an autoimmune disease that causes the body's immune system to attack and destroy insulin-producing beta cells in the pancreas. Traditional management of type 1 diabetes has primarily involved replacing the missing insulin with injections which, though effective, can be expensive and burdensome.

new study suggests that an existing drug could be repurposed to treat type 1 diabetes, potentially reducing dependence on insulin as the sole treatment.

The research centers on a medication known as α-difluoromethylornithine (DFMO), which inhibits an enzyme that plays a key role in cellular metabolism. The latest translational results are a culmination of years of research: In 2010, the lab performed fundamental biochemistry experiments on beta cells in culture. They found that suppressing the metabolic pathway altered by DFMO helped protect the beta cells from environmental factors, hinting at the possibility of preserving and even restoring these vital cells in patients diagnosed with type 1 diabetes.

The researchers confirmed their observations preclinically in zebrafish and then in mice and launched a clinical trial to evaluate the safety and tolerability of the drug in type 1 diabetes patients. The results of the trial indicated that the drug is safe for type 1 diabetes patients and can help keep insulin levels stable by protecting beta cells.

Importantly, DFMO has already been FDA-approved as a high dose injection since 1990 for treating African Sleeping Sickness and received breakthrough therapy designation for neuroblastoma maintenance therapy after remission in 2020. Pre-existing regulatory approval could potentially facilitate its use in type 1 diabetes, saving effort and expense and getting the treatment to patients sooner.

“For a drug that’s already approved for other indications, the approval timeline can be a matter of years instead of decades once you have solid clinical evidence for safety and efficacy,” said the author. “Using a new formulation of DFMO as a pill allows patients to take it by mouth instead of needing to undergo regular injections, and it has a very favorable side effect profile. It’s exciting to say we have a drug that works differently from every other treatment we have for this disease.”