What is SS-31?
SS-31 (Elamipretide, also known as MTP-131 or Bendavia) is a tetrapeptide with the sequence D-Arg-Dmt-Lys-Phe-NH2, where Dmt is 2’,6’-dimethyltyrosine. It was designed by Hazel Szeto and Peter Schiller to selectively penetrate mitochondria and bind to a specific lipid in the inner mitochondrial membrane.
Why SS-31 is unique: cardiolipin
SS-31 binds with high selectivity to cardiolipin, a phospholipid found almost exclusively in the inner mitochondrial membrane that is essential for the function of the electron transport chain (ETC).
In aged, ischemic, or mitochondrially dysfunctional cells:
- Cardiolipin is oxidized and its structure is altered.
- This destabilizes ETC complexes I, III, and IV and the supercomplexes that organize them.
- ATP production falls and reactive oxygen species (ROS) generation increases.
SS-31 binds to cardiolipin and:
- Protects it from oxidation.
- Stabilizes ETC supercomplexes.
- Restores electron flow and ATP production.
- Reduces ROS generation.
Active clinical trials
Heart failure with reduced ejection fraction (HFrEF):
- PROGRESS-HF study: SS-31 IV improved 6-minute walk distance and cardiac function parameters in Phase 2.
Acute ischemic kidney injury:
- Multiple studies show renal protection in ischemia-reperfusion contexts (cardiac surgery, transplantation).
Barth syndrome (pediatric mitochondrial disease):
- NEJM 2021: SS-31 (elamipretide) significantly improved motor function and quality of life in children with Barth syndrome — a rare disease caused by mutations in the cardiolipin gene.
Leber hereditary optic neuropathy:
- In Phase 2 trials for this mitochondrial vision disease.
Relevance in longevity
Mitochondrial dysfunction is one of the “Hallmarks of Aging.” SS-31 offers the possibility of restoring mitochondrial function in aged tissues, not just in rare diseases — making it relevant to anti-aging medicine.
Studies in old mice show rejuvenation of renal, cardiac, and muscle function with SS-31, comparable to young animals.
In active clinical development. For research use only. Results are promising across multiple indications. Not yet approved. Research use only under medical supervision.
Reported protocol (research reference)
| Vial sizes | 10 mg, 30 mg, 50 mg |
|---|---|
| Reported dose | Clinical trials: 0.05–0.25 mg/kg IV or SC depending on indication. No approved protocol for general use. |
| Half-life | ~3–4 hours. |
| FDA status | Investigational |