In-depth entry

SS-31 (Elamipretide)

also known as: Elamipretide, Forzinity, Bendavia, MTP-131

The first FDA-approved mitochondria-targeted peptide therapeutic — approved September 2025 as Forzinity for Barth syndrome, with broader investigation in heart failure, macular degeneration, and aging.

A 4-amino-acid aromatic-cationic peptide (D-Arg-Dmt-Lys-Phe-NH2) that concentrates in the inner mitochondrial membrane (1000-fold over cytosol) by binding cardiolipin, stabilizing mitochondrial cristae architecture and restoring ATP production — FDA-approved in 2025 for Barth syndrome.

Mechanism of action

Selectively binds cardiolipin — a unique phospholipid found almost exclusively in the inner mitochondrial membrane — stabilizing cristae architecture and protecting the electron transport chain. Restores normal cardiolipin remodeling in Barth syndrome (where tafazzin mutations cause abnormal cardiolipin composition). Downstream effects include restored ATP synthesis, reduced reactive oxygen species generation, and preserved mitochondrial membrane potential. In Barth syndrome, this translates to improved muscle strength via restored mitochondrial function in skeletal and cardiac muscle.

Primary uses

Barth syndrome (FDA-approved, Forzinity)
Primary mitochondrial myopathy (investigational)
Dry age-related macular degeneration (investigational)
Heart failure (Phase 2/3, mixed results)
Ischemia-reperfusion injury research

Typical dosing

40 mg once daily (subcutaneous)

Forzinity: 40 mg SC once daily for adult and pediatric patients ≥30 kg. Adverse events primarily injection site reactions and rare hypersensitivity.

Regulatory status

FDA granted accelerated approval September 19, 2025 as Forzinity (Stealth BioTherapeutics) for improvement of muscle strength in adult and pediatric patients with Barth syndrome weighing ≥30 kg. This is the first FDA-approved mitochondria-targeted therapeutic. Continued approval contingent on confirmatory trials. Additional indications under investigation: primary mitochondrial myopathy, dry age-related macular degeneration.

References

[fda-pi] Forzinity (elamipretide) Prescribing Information. Stealth BioTherapeutics. September 2025.
[clinical-trial] Thompson WR, et al. "A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER)." Genet Med, 2021;23:471-478.
[pubmed] Birk AV, et al. "The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin." J Am Soc Nephrol, 2013;24:1250-1261.
[clinical-trial] Butler J, et al. "Effects of elamipretide on left ventricular function in heart failure with reduced ejection fraction: the PROGRESS-HF phase 2 trial." J Card Fail, 2020.

Related peptides

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MOTS-c

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Humanin

A mitochondrial-derived peptide with neuroprotective, metabolic, and anti-apoptotic activity — one of the first signaling peptides identified as encoded by mitochondrial DNA.

FOXO4-DRI

A D-retro-inverso cell-penetrating peptide designed by the Peeper lab (Netherlands Cancer Institute) to selectively clear senescent cells — the prototype senolytic peptide.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.