Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy - PubMed
14 hours ago
- #iPSCs
- #mitochondrial disease
- #drug repurposing
- Pluripotent stem-cell-based screening identified sildenafil as a potential therapy for mitochondrial diseases, particularly Leigh syndrome (LS).
- Sildenafil, a PDE5 inhibitor, was prioritized due to its clinical safety profile and ability to correct mitochondrial membrane potential defects.
- The drug restored neurodevelopmental pathways and normalized calcium responses in LS brain organoids.
- In animal models of LS, sildenafil extended lifespan and improved disease phenotypes.
- Off-label treatment in six LS patients showed improved motor function and resistance to metabolic crises.
- The study highlights the potential of iPSC-driven drug discovery for mitochondrial diseases.