What Is SS-31? Benefits, Research & Safety

SS-31 was developed by Hazel Szeto and Peter Bhatt Schiller at Weill Cornell Medical College in the early 2000s. The SS peptide series was designed using alternating aromatic-cationic motifs that enable mitochondrial targeting without requiring the typical mitochondrial targeting sequence. The key innovation was the discovery that small, cell-permeable peptides with the right structural features could selectively concentrate in mitochondria at 1,000-5,000 fold higher concentrations than in the cytoplasm. SS-31 was identified as the most promising candidate. Preclinical studies showed remarkable effects: protection against ischaemia-reperfusion injury, reversal of age-related mitochondrial dysfunction in animal models, and improvements in cardiac function. These results generated significant excitement about mitochondria-targeted therapy. Stealth BioTherapeutics was founded to develop SS-31 (as elamipretide) clinically. The company conducted multiple clinical trials across several disease areas. While some trials showed positive signals, the pivotal MMPOWER-3 trial in primary mitochondrial myopathy did not meet its primary endpoint in 2020, though subgroup analyses suggested benefits in certain patient populations. Development continues, with focus on Barth syndrome (which received FDA Fast Track designation) and other mitochondrial conditions.