SS-31: Complete Guide

SS-31 belongs to the Szeto-Schiller (SS) peptide class — aromatic-cationic peptides that selectively accumulate in mitochondria independent of mitochondrial membrane potential. This selectivity is remarkable: SS-31 concentrates ~5,000-fold in the inner mitochondrial membrane compared to cytoplasmic concentrations.

The clinical development of SS-31 (as elamipretide) has advanced furthest among mitochondria-targeted therapies. Stealth BioTherapeutics (now Larimar Therapeutics) conducted clinical trials for multiple indications related to mitochondrial dysfunction, and the compound received both Breakthrough Therapy and Fast Track designations from the FDA for Barth syndrome (a rare genetic mitochondrial disease).

• Cardiolipin stabilization: SS-31 binds to cardiolipin, a phospholipid found exclusively in the inner mitochondrial membrane. Cardiolipin is essential for the structural organization and function of electron transport chain complexes. Age and disease cause cardiolipin peroxidation and dysfunction.
• Electron transport optimization: By stabilizing cardiolipin, SS-31 optimizes electron transfer between respiratory complexes, improving ATP production efficiency
• ROS reduction: Improved electron transport reduces electron leakage and superoxide production — reducing oxidative stress at its source
• Mitochondrial bioenergetics: Restores mitochondrial membrane potential and ATP synthesis capacity in dysfunctional mitochondria

• Barth syndrome: FDA Breakthrough Therapy designation. Phase 2/3 trials showed improvements in the 6-minute walk test and cardiac function in Barth syndrome patients
• Heart failure: Phase 2 trials (EMBRACE) in patients with heart failure showed improvements in left ventricular volumes, though primary endpoints in larger trials were mixed
• Primary mitochondrial myopathy: Improvements in exercise tolerance and fatigue scores
• Age-related macular degeneration: Phase 1/2 trials explored subcutaneous elamipretide for geographic atrophy

Clinical trial dosing:

• Subcutaneous: 40 mg daily (clinical trial dose for Barth syndrome)
• IV (acute settings): 0.05 mg/kg/hour infusion (heart failure trials)
• Research: 0.5–5 mg subcutaneous (extrapolated from animal studies)

Use the peptide calculator for reconstitution of research-grade material.

• Injection site reactions: Most common adverse event in clinical trials
• Generally well-tolerated across multiple clinical trials
• No significant cardiac safety signals in heart failure patients (an important finding given the cardiac indication)
• Mild headache reported in some trial participants