SS-31 (Elamipretide)

Nine publications are cited, all from 2023 to 2026. Three are clinical and come from two trial programmes: the 168-week open-label extension of TAZPOWER in Barth syndrome, the phase 3 MMPOWER-3 randomised trial in primary mitochondrial myopathy, and a post hoc genotype analysis of MMPOWER-3. The other six are preclinical, covering target identification, cardiomyocytes under hypoxia and reoxygenation, ozone-induced airway injury, pulmonary fibrosis, spinal cord injury and cerebral microhaemorrhages in ageing.

The TAZPOWER extension reported sustained tolerability over 168 weeks, with gains on functional assessments and in cardiac function. MMPOWER-3 reported no gain on the six-minute walk test or the PMMSA total fatigue score, while reporting the drug as well tolerated; the post hoc analysis then described a response in patients with mtDNA replisome disorders. In the laboratory, a genome-wide CRISPR screen identified phospholipid scramblase 3 as the target required for SS-31's mitochondrial protection in cells and in animals. Other models reported lower oxidative stress and suppression of inflammatory and pyroptotic pathways driven by PI3K/AKT after ozone exposure, reduced Nrf2-dependent NLRP3 inflammasome activity in macrophages in pulmonary fibrosis, and less pyroptosis after spinal cord injury, linked to cPLA2 and lysosomal membrane permeabilisation. A construct joining SS-31 to Fer-1 suppressed ferroptosis in cardiomyocytes after hypoxia and reoxygenation.

The clinical evidence is small and mixed. MMPOWER-3 reported no gain on its walking and fatigue measures, the positive subgroup result is post hoc, and the TAZPOWER extension was open-label, so participants and investigators knew the drug was being given. Each preclinical model is represented by a single study, and one of them reports a conclusion that is not about SS-31's effect: the microhaemorrhage paper centres on an imaging method and a call for multi-targeted approaches. The cardiomyocyte work tested a conjugate rather than SS-31 alone.