This research study identifies sildenafil as a potential treatment for Leigh syndrome, a currently untreatable and severe mitochondrial disorder. By screening thousands of existing drugs on patient-derived stem cells, scientists discovered that this PDE5 inhibitor can correct cellular defects, such as abnormal mitochondrial membrane potential and impaired calcium regulation. The drug demonstrated significant efficacy in both human brain organoids and animal models, where it successfully extended lifespan and improved neurological development. Furthermore, off-label clinical use in six patients resulted in enhanced motor function and greater resilience against metabolic crises. These findings suggest that repurposing sildenafil could offer a life-changing therapeutic strategy for individuals suffering from various forms of mitochondrial disease.

References:

• Zink A, Dai D F, Wittich A, et al. Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy[J]. Cell, 2026.