SS-31

SS-31 (Elamipretide) is a synthetic tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2',6'-dimethyltyrosine. Developed by Dr. Hazel Szeto at Weill Cornell Medicine, it belongs to the Szeto-Schiller (SS) peptide family designed to concentrate in mitochondria approximately 1000-5000 fold compared to extracellular concentrations due to their alternating aromatic-cationic motif.

SS-31 selectively accumulates in the inner mitochondrial membrane where it binds to cardiolipin, a phospholipid essential for cristae structure and the organization of electron transport chain complexes. By stabilizing cardiolipin interactions with cytochrome c, SS-31 optimizes electron transfer, improves ATP production, and reduces electron leak that generates reactive oxygen species. Importantly, it restores mitochondrial function in aged or damaged mitochondria without affecting healthy mitochondria.

Clinical development has progressed through multiple Phase II and Phase III trials. Studies in primary mitochondrial myopathy (MMPOWER trials) showed improvements in the 6-minute walk test. Research in heart failure (PROGRESS-HF) demonstrated improved left ventricular function. In age-related mitochondrial dysfunction, SS-31 restored ATP production and reduced oxidative damage in skeletal muscle of elderly subjects. The peptide has also shown promise in acute kidney injury, ischemia-reperfusion injury, and Barth syndrome. Its unique mechanism of targeting the fundamental bioenergetic machinery makes it relevant across a wide range of age-related and mitochondrial diseases.