Diabetes and DFMO the Wonder Drug

The small molecule drug α-difluoromethylornithine (DFMO) first secured FDA approval in 1990 as an injectable against African sleeping sickness. Thirty years later, it earned a breakthrough therapy designation for its role in neuroblastoma maintenance therapy post-remission. Now, researchers from Indiana University (IU) School of Medicine and the University of Chicago Medicine suggest DFMO could be repurposed for type 1 diabetes.

The drug functions by blocking the first step in the polyamine biosynthetic molecular pathway – a route previous research found to have adverse effects on an inflammatory environment akin to the beta cell environment in type 1 diabetes development.

“One thing that was really appealing to us about DFMO was that it has already been studied in other contexts,” said Emily Sims, Associate Professor of Pediatrics at IU School of Medicine and a pediatric endocrinologist at Riley Children’s Health. “Our initial safety study in individuals with recent-onset type 1 diabetes demonstrated the drug’s excellent tolerance across various doses. Those receiving higher doses exhibited increased C-peptide levels compared to individuals treated with placebo, indicating enhanced natural insulin production.”

In a three-month randomized controlled trial involving 41 participants with recent onset type 1 diabetes, DFMO successfully met its primary safety and tolerability outcome. It also lowered urinary putrescine levels and, at higher doses, maintained C-peptide area under the curve without leading to immune modulation. Examining DFMO-treated human islets exposed to cytokine stress revealed additional alterations in mRNA translation, nascent protein transport, and protein secretion, suggesting that DFMO may safeguard β cell function in T1D through islet cell-autonomous effects.

“The type 1 diabetes treatment we’re evaluating comes in oral form,” Sims adds. “Unlike many existing disease-modifying drugs that necessitate injection or IV administration, an oral medication can enhance user-friendliness and broaden accessibility, making it more feasible and appealing to a wider range of individuals.”