SS-31

In a review synthesising preclinical and clinical work, SS-31 (elamipretide) has been characterised as a mitochondria-targeting tetrapeptide that binds cardiolipin in the inner mitochondrial membrane, and has been studied in models of heart failure, neurodegeneration, ischemia-reperfusion injury, metabolic syndromes, and muscle atrophy, with cristae stabilisation, oxidative-stress reduction, and ATP-related changes described as reported mechanisms.[1]

In the MMPOWER-3 phase-3 randomised, double-blind, placebo-controlled trial in adults with genetically confirmed primary mitochondrial myopathy, subcutaneous elamipretide was evaluated against placebo over 24 weeks using the 6-minute walk test and Primary Mitochondrial Myopathy Symptom Assessment fatigue score as primary endpoints.[2]

In the 168-week open-label extension of the TAZPOWER trial in individuals with Barth syndrome, daily subcutaneous elamipretide was assessed for long-term safety and tolerability alongside changes in the 6-minute walk test, fatigue scores, muscle strength, echocardiographic parameters, and cardiolipin-related biomarkers, with injection-site reactions reported as the most common adverse events.[3]

In a review synthesising the past decade of mechanistic work, elamipretide's cardiolipin-binding properties have been characterised as influencing mitochondrial membrane electrostatic potentials and the assembly of cardiolipin-dependent proteins, expanding earlier descriptions of a reactive-oxygen-species-scavenging mechanism toward broader effects on mitochondrial bioenergetics.[4]