SS-31 / Elamipretide
Elamipretide (D-Arg-2',6'-dimethylTyr-Lys-Phe-NH2; aka Bendavia, MTP-131, SS-31)
Aromatic-cationic tetrapeptide developed by Stealth BioTherapeutics that selectively binds cardiolipin in the inner mitochondrial membrane. Stabilizes the electron transport chain, reduces ROS leak, and improves ATP production. Mixed pivotal-trial history: phase 3 MMPOWER-3 in primary mitochondrial myopathy MISSED its primary endpoints (6MWT and PMMSA fatigue) at week 24 in 2020. Phase 2 ReCLAIM-2 in dry AMD with geographic atrophy MISSED its primary endpoint (BCVA + GA area) in 2024 but showed strong EZ-preservation secondaries that became the basis for ongoing phase 3 ReNEW/ReGAIN trials. Mechanism remains scientifically interesting; clinical efficacy for general longevity use is unproven.
At a glance
- Half-life
- ~2 h Plasma t½ ~2 hours after SC injection in healthy volunteers; mitochondrial residence time much longer due to membrane sequestration. Bioavailability ~85% SC. Tmax ~1.5h.
- Routes
- SubQ · IV
- Vial sizes
- 40 mg · 50 mg
- Evidence base
- 3 studies 2 human · 1 preclinical
Mechanism
Concentrates >1000x in the inner mitochondrial membrane via electrostatic and hydrophobic interactions with cardiolipin. By stabilizing cardiolipin–cytochrome c interactions, it preserves electron transport chain super-complexes, reduces electron leak (ROS), prevents cytochrome c release / apoptosis, and improves ATP synthesis. Cell-permeable; does not depolarize the mitochondrial membrane. Phase 3 MMPOWER-3 in primary mitochondrial myopathy MISSED primary endpoints (6MWT + fatigue) at week 24. ReCLAIM-2 in AMD geographic atrophy MISSED primary endpoint but showed 43% EZ-attenuation reduction on secondaries.
Dosing
Any amounts shown here are reported from published studies only. 2 of 3 catalogued studies involved human subjects. COMPOUND does not publish its own dosing guidance.
Where a study reports an amount, it appears in that study's entry below, attributed to the source.
Published evidence
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Human RCT 2024
ReCLAIM-2: Randomized Phase II Trial Evaluating Elamipretide in AMD Geographic Atrophy
40mg SC daily for 48 weeks. MISSED primary (LL BCVA + GA area). Showed 43% reduction in EZ attenuation and 14.6% vs 2.1% achieving >10 letter gain on secondaries: basis for phase 3 ReNEW/ReGAIN.
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Human RCT 2023
Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy
Phase 2 dose-finding supported 40mg dose. Phase 3 MMPOWER-3 (2020) subsequently MISSED primary endpoints (6MWT and PMMSA fatigue) at week 24: failed primary indication.
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Animal in vivo 2013
The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin
Established cardiolipin-binding mechanism: SS-31 protects mitochondrial cristae structure and restores ATP production after ischemia-reperfusion injury.
Reported side effects
- Injection site reaction
- Very common Mild · Most common AE in trials: 86% in elamipretide arm vs 71% placebo in ReCLAIM-2. Self-resolving.
- Erythema / pruritus at injection site
- Common Mild · Histamine-like local response.
- Headache
- Occasional Mild · Reported across trials.
- Nausea
- Occasional Mild · Reported infrequently.
Interactions
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CoQ10 Synergy
Both support mitochondrial function via different mechanisms (cardiolipin stabilization vs ETC electron carrier). Likely synergistic; commonly stacked in clinical mitochondrial cocktails.
Reconstitution and storage
Often supplied as ready-to-inject solution in clinical trials. Research peptide vials require BAC water reconstitution: 40mg + 1.6mL → 25 mg/mL.
Reconstituted solution stable refrigerated for ~30 days. Avoid freeze-thaw cycles.