A decades-old medication, difluoromethylornithine (DFMO or eflornithine), traditionally used for treating West African sleeping sickness, reducing unwanted facial hair in women, and preventing neuroblastoma recurrence, is now showing potential in addressing Bachmann-Bupp syndrome (BABS), an ultra-rare life-threatening genetic disorder. Affecting only about 20 individuals worldwide, BABS arises from gain-of-function mutations in the ornithine decarboxylase (ODC1) gene, leading to severe developmental delays, hypotonia, alopecia, and other debilitating symptoms. Researchers at Corewell Health and Michigan State University, led by pediatric geneticist Caleb Bupp, MD, and pediatrics professor André Bachmann, PhD, discovered that DFMO inhibits the ODC protein, counteracting the excessive enzyme activity caused by these mutations. Initial treatments under FDA-approved single-patient protocols have yielded encouraging results in a handful of patients, including improvements in muscle tone and developmental milestones. This breakthrough stems from a serendipitous collaboration between the experts, building on Bachmann’s three decades of research on DFMO’s effects on the ODC1 pathway, originally in pediatric neuroblastoma contexts.

Despite these early successes, advancing DFMO for BABS faces significant hurdles due to the disease’s rarity, which complicates patient recruitment, awareness, and large-scale clinical trials. Regulatory complexities and the need for robust preclinical data have stalled progress, with the FDA urging formal trials but key challenges like defining endpoints persisting. A new partnership with Every Cure, a nonprofit biotech organization dedicated to drug repurposing, is poised to accelerate momentum. Every Cure is supporting preclinical studies, retrospective analyses, regulatory navigation, and awareness campaigns among physicians and rare disease networks to ensure undiagnosed children are identified and treated. As noted by Every Cure’s co-founder David Fajgenbaum, MD, this collaboration aims to bridge evidence gaps and facilitate broader access. With preclinical work slated for next year, this initiative highlights the value of repurposing existing drugs for orphan diseases, offering hope for personalized therapies in pediatric genetics. For Indian doctors managing rare pediatric cases, this underscores the importance of genetic screening for ODC1 mutations and considering off-label uses of approved drugs like DFMO, potentially in collaboration with global networks to overcome similar barriers in resource-limited settings.