SS-31 (elamipretide) is a cell-permeable tetrapeptide with a unique mechanism of action that targets mitochondrial dysfunction. The peptide selectively accumulates in the inner mitochondrial membrane, where it binds to cardiolipin, a specialized phospholipid essential for organizing electron transport chain supercomplexes and maintaining the structure of mitochondrial cristae. By stabilizing cardiolipin–protein interactions, SS-31 optimizes electron transport efficiency, reduces the pathological generation of reactive oxygen species (ROS), and enhances ATP synthesis in metabolically active tissues.
Preclinical research has demonstrated that SS-31 protects against mitochondrial dysfunction across multiple disease models, including heart failure, ischemia-reperfusion injury, neurodegenerative disorders, chronic kidney disease, and age-related muscle atrophy. In human clinical trials, SS-31 showed a favorable safety and tolerability profile with no dose-limiting toxicities. Although Phase II trials in heart failure and primary mitochondrial myopathy did not meet their primary efficacy endpoints, the TAZPOWER trial in Barth syndrome demonstrated significant improvements in muscle strength and six-minute walk distance, leading to FDA Accelerated Approval in 2025.
