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Mitochondria-targeted tetrapeptide (cardiolipin-binding Szeto-Schiller peptide)

Elamipretide

Approvedaka SS-31, MTP-131, Bendavia, Forzinity

Elamipretide is designed to improve mitochondrial function by stabilising cardiolipin and the cristae architecture of the inner mitochondrial membrane. It has been evaluated across numerous conditions such as primary mitochondrial myopathy, Barth syndrome, Leber hereditary optic neuropathy, dry age-related macular degeneration and heart failure, with mixed results; its pivotal primary mitochondrial myopathy trial (MMPOWER-3) did not meet its primary endpoint. In September 2025 it received US FDA accelerated approval for Barth syndrome (as Forzinity) based on an improvement in knee-extensor muscle strength, with a confirmatory trial required; for all other indications it remains investigational.

Mechanism

In plain terms, elamipretide is a small peptide that concentrates inside mitochondria, the cell's energy-producing structures, and helps them make energy more efficiently while producing less oxidative stress. Technically, it is a cell-permeable, positively charged tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that accumulates in the inner mitochondrial membrane and binds the phospholipid cardiolipin. By stabilising cardiolipin and cristae structure it is reported to improve electron-transport-chain efficiency and ATP production and to reduce reactive oxygen species, rather than acting on a conventional cell-surface receptor.

Regulatory Status by Region

  • United States (FDA)Granted accelerated approval on September 19, 2025 as Forzinity (elamipretide HCl) to improve muscle strength in adult and paediatric patients with Barth syndrome who weigh at least 30 kg, based on an intermediate endpoint (knee-extensor muscle strength) with a confirmatory trial required. It is not approved for any other indication, and the pivotal primary mitochondrial myopathy trial (MMPOWER-3) did not meet its primary endpoint.
  • Australia (TGA)Not on the ARTG; investigational only and not approved for supply.
  • European Union (EMA)No EMA marketing authorisation; not authorised as a medicine in the EU.
  • WADANot listed by name on the Prohibited List; athletes should verify current status with their anti-doping organisation.

Key Studies

  • Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy (Karaa A, Haas R, Goldstein A, Vockley J, Weaver WD, Cohen BH. Neurology. 2018;90(14):e1212-e1221. PMID 29500292)
  • First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics (Szeto HH. Br J Pharmacol. 2014;171(8):2029-2050. PMID 24117165)

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