SS-31 (Elamipretide)

Also known as: Elamipretide, MTP-131, Bendavia

**Mechanism of Action** SS-31 (Elamipretide) is a mitochondria-targeting tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH₂) that selectively binds to cardiolipin, a phospholipid enriched in the inner mitochondrial membrane. This interaction stabilizes the cristae structure, enhances electron transport chain efficiency, and restores ATP synthesis under oxidative stress. By reducing mitochondrial reactive oxygen species (ROS) production and preventing cytochrome c release, SS-31 mitigates apoptosis and preserves cellular bioenergetics. **Key Research Findings** Preclinical studies demonstrate SS-31 improves mitochondrial function in models of ischemia-reperfusion injury, heart failure, and neurodegenerative diseases. In phase II clinical trials (e.g., EMBRACE-HF, PROGRESS-HF), intravenous SS-31 reduced left ventricular end-diastolic volume and improved exercise tolerance in heart failure with reduced ejection fraction (HFrEF). A phase II trial in primary mitochondrial myopathy (MM) showed trends toward improved 6-minute walk distance and fatigue scores, though primary endpoints were not met. Ongoing phase III trials (e.g., MMPOWER-3) are evaluating efficacy in MM and other mitochondrial disorders. **Clinical Relevance** SS-31 is the first cardiolipin-targeting therapeutic to reach advanced clinical testing, with potential applications in heart failure, mitochondrial myopathy, and age-related metabolic decline. Its favorable safety profile (mild injection-site reactions) supports further development. If approved, it would represent a novel class of mitochondrial stabilizers for diseases with bioenergetic dysfunction. For research purposes only — not medical advice.

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