Encyclopedia

SS-31 (elamipretide) is a mitochondria-targeted tetrapeptide that binds and stabilizes cardiolipin in the inner mitochondrial membrane, improving mitochondrial function and reducing reactive oxygen species. It is an investigational drug (developed by Stealth BioTherapeutics) studied in mitochondrial diseases such as Barth syndrome, mitochondrial myopathy, and Friedreich's ataxia, as well as dry age-related macular degeneration. It is not FDA-approved.

SS-31 (elamipretide; development codes MTP-131, Bendavia) is a small aromatic-cationic tetrapeptide, D-Arg-Dmt-Lys-Phe-NH2 (where Dmt is 2,6-dimethyltyrosine), with limited blood-brain-barrier penetration. It concentrates in the inner mitochondrial membrane and binds cardiolipin, stabilizing membrane structure and the electron transport chain, thereby improving mitochondrial energetics and reducing toxic reactive oxygen species. In animal and cellular models it has reversed mitochondrial fragmentation and markers of disease in mitochondrial cardiomyopathies, Friedreich's ataxia, Barth syndrome, and ischemia-reperfusion injury, and it also suppresses macrophage activation and inflammasome signaling. It has been generally well tolerated in clinical trials with preliminary signs of benefit, but it remains investigational and is not FDA-approved.

Mechanism of Action

Concentrates in the inner mitochondrial membrane and binds cardiolipin, stabilizing membrane architecture and the electron transport chain. This improves mitochondrial respiration and ATP production and reduces reactive oxygen species (ROS). Secondary anti-inflammatory effects include suppression of the Nrf2-dependent NLRP3 inflammasome and M1 macrophage polarization via ROS scavenging.