SS-31

SS-31 (elamipretide, Bendavia, MTP-131) is a mitochondria-targeted tetrapeptide developed at Weill Cornell Medical College that selectively concentrates in the inner mitochondrial membrane, binding to cardiolipin — a unique phospholipid essential for electron transport chain complex organization and function. By stabilizing cardiolipin-protein interactions, SS-31 restores efficient mitochondrial electron transport, reduces ROS production, and improves ATP synthesis. SS-31 has undergone extensive clinical trials for heart failure (EMBRACE trial), mitochondrial myopathy (MMPOWER trials), and Barth syndrome. Its ability to directly target mitochondrial dysfunction addresses a fundamental mechanism underlying aging, neurodegeneration, cardiomyopathy, and metabolic disease.

SS-31's alternating aromatic-cationic motif (Arg-Dmt-Lys-Phe) enables selective accumulation in the inner mitochondrial membrane (1000-5000 fold concentration over cytoplasm). It binds cardiolipin, stabilizing its interactions with cytochrome c and electron transport chain complexes (I, III, IV). This optimizes electron flow, reduces electron leak and superoxide generation, maintains mitochondrial membrane potential, and enhances ATP production efficiency.

Heart Failure EMBRACE-STEMI trial showed reduced infarct size. PROGRESS-HF studied for chronic heart failure. Mixed clinical results but consistent improvement in mitochondrial biomarkers. Mitochondrial Myopathy MMPOWER trials for primary mitochondrial myopathy showed improvements in 6-minute walk test. Barth Syndrome Targets the cardiolipin deficiency central to this genetic mitochondrial disease. Age-Related Diseases Mitochondrial dysfunction underlies many aging pathologies — SS-31 addresses this root cause.

Cardiolipin stabilization in inner mitochondrial membrane. Electron transport chain optimization. Reduced ROS from Complex I and III. Maintained mitochondrial membrane potential (ΔΨm). Enhanced ATP synthase (Complex V) activity.

Generally well-tolerated in clinical trials. Injection site reactions. Transient headache. No serious adverse effects in Phase 1-3 studies. Long-term safety data limited.

Supplied as lyophilized powder or solution for injection. Store at -20°C (powder) or 2-8°C (solution). The D-Arg modification provides protease resistance. Good aqueous solubility. Stable at physiological pH.

Investigational. Multiple Phase 2/3 trials completed (Stealth BioTherapeutics). Orphan drug designation for Barth syndrome. Not yet FDA-approved. Not WADA-prohibited.