SS-31 (Elamipretide)

HFpEF rats had reduced skeletal muscle cardiolipin levels (-6.8%, P=0.007) and impaired cardiolipin maturation (tafazzin expression), alongside contractile dysfunction, titin hyperphosphorylation, fiber atrophy, and increased oxidative stress markers.; Elamipretide improved whole-muscle contractile function (soleus +8.2%, P=0.041; extensor digitorum longus +10.9%, P=0.016) and single-fiber function (soleus +173.2%, P<0.001; EDL +66.0%, P=ns).; Elamipretide reduced titin phosphorylation (soleus -35.4%, EDL -40.2%, both P<0.001) and prevented atrophy (soleus +49%, P=0.001; EDL +54.8%, P<0.001).; Improved mitochondrial function, presumably via cardiolipin-mediated improvements in oxidative phosphorylation, may be associated with muscle force and cardiolipin integrity, supporting cardiolipin stabilization as a therapeutic target.

First reported case of elamipretide use in a preschool-aged child with Barth syndrome outside the United States.; LVEF improved from 20% to 50% and mitral regurgitation decreased from moderate-to-severe to mild over six months.; Functional capacity, nutritional status, and health-related quality of life improved, with return to full-time school and temporary suspension from the transplant list.; Treatment was generally well tolerated; one transient, non-serious episode of abdominal pain with moderate pancreatic enzyme elevation resolved without discontinuation.

Two FDA approvals emerged within one year for mitochondrial diseases: elamipretide (Forzinity) for Barth syndrome and deoxynucleoside therapy (Kygevvi) for TK2 deficiency.; Another mitochondrial disease therapy is currently under review.; Zink et al. suggest sildenafil (Viagra) could treat Leigh syndrome.; This highlights drug repurposing for severe pediatric mitochondrial disease.

Elamipretide is a mitochondrial cardiolipin binder developed by Stealth BioTherapeutics.; Approved in the USA in September 2025 for improving muscle strength in Barth syndrome patients weighing ≥30 kg.; First disease-specific treatment for Barth syndrome, an ultra-rare X-linked recessive disorder.; Also in phase III development for dry age-related macular degeneration and mitochondrial myopathies.

Elamipretide is the first cardiolipin-directed mitochondrial therapeutic and the first FDA-approved therapy for Barth syndrome, granted accelerated approval on September 19, 2025.; The randomized, double-blind, placebo-controlled crossover trial showed no significant improvement in 6-minute walk test or fatigue scores.; Sustained benefits were observed during a 168-week open-label extension.; The most common adverse events were mild injection-site reactions, and a confirmatory trial is required as a condition of accelerated approval.

What is SS-31 (Elamipretide)?

**Mechanism of Action** SS-31 (Elamipretide) is a mitochondria-targeting tetrapeptide (D-Arg-dimethylTyr-Lys-Phe-NH₂) that selectively binds to cardiolipin, a phospholipid enriched in the inner mitochondrial membrane. This interaction stabilizes the cristae structure, optimizes electron transport chain supercomplex ass

How does SS-31 (Elamipretide) work?

Mitochondria-targeting tetrapeptide that binds cardiolipin on the inner membrane to stabilize cristae and restore ATP production.

What is the research status of SS-31 (Elamipretide)?

SS-31 (Elamipretide) is currently classified as clinical trials, with 222 research references on record. This is for research purposes only and is not medical advice.

What is the molecular weight of SS-31 (Elamipretide)?

SS-31 (Elamipretide) has a molecular weight of approximately 639.8 g/mol (formula C32H49N9O5).