Prevention and Therapeutic Development in Mitochondrial Disease: A Review of Recent Real-World Clinical Evidence

Although individually rare, primary mitochondrial diseases (PMD) collectively represent a substantial cause of inherited metabolic and multisystem diseases. Advances in genomic testing have broadened the recognized spectrum of mitochondrial diseases and improved molecular diagnosis, while progress in disease modeling has accelerated therapeutic development. Concurrently, an expanding body of clinical research has evaluated supportive, pharmacological, preventive, and emerging advanced interventions across genetically and clinically heterogeneous mitochondrial disease subtypes. However, the available evidence remains fragmented, with considerable variability in study design, patient selection, outcome measures, and follow-up duration. In this review, we summarize recent therapeutic and preventive interventions for PMD, including supplement and dietary strategies, mechanism-based drug therapies, reproductive prevention approaches for mitochondrial DNA disease, and emerging advanced therapies such as gene, cell, and enzyme-based treatments. We also examine the strengths and limitations of the current evidence base and discuss implications for clinical practice, trial design, and future translational research.