SS-31
Tetrapeptide targeting the mitochondrial inner membrane (elamipretide)
In September 2025, the FDA approved elamipretide (SS-31) in the United States: according to its manufacturer, the first mitochondria-targeting molecule to be approved.
This four-amino-acid peptide crosses the cell membrane and binds cardiolipin, the lipid of the inner mitochondrial membrane that keeps the respiratory chain assembled, the chain that makes ATP. In the laboratory, it concentrates there about 1,000 times more than in the fluid around the cells (Zhao, 2004).
It is studied for the tissues that use the most energy: the FDA approval rests on muscle strength, and in the ReCLAIM-2 trial (2025), loss of the retina's ellipsoid zone was reduced by 43%.
- Half-life
- A few hours in the blood; the peptide accumulates in the mitochondria, where its structural effect lasts much longer.
- Route
- Subcutaneous injection, the route used in clinical trials.
Technical sheet
- Family
- Tetrapeptide targeting the mitochondrial inner membrane (elamipretide)
- Half-life
- A few hours in the blood; the peptide accumulates in the mitochondria, where its structural effect lasts much longer.
- Route
- Subcutaneous injection, the route used in clinical trials.
- Time to effect
- Energy and recovery reported by users in two to four weeks; in the trials, the measured effects build over several months.
- Level of evidence
- Documented in humans : In humans: mitochondrial diseases, heart failure and the retina. Day-to-day energy comes from user reports: in 218 adults with a mitochondrial myopathy, fatigue did not differ from placebo.
Chemical identity
- Chemical name
- Élamipretide
- Form
- Synthetic peptide, values for the base form
- CAS No.
- 736992-21-5
Salt form: as stated on the lot's certificate of analysis.
Cardiolipin, a lipid of the inner membrane
Cardiolipin keeps the complexes of the respiratory chain assembled, the chain that makes ATP in the cristae of the inner membrane. With age, oxidative stress, or disease, it oxidizes: the cristae become disorganized, energy drops, and free radicals leak.
Selective binding to cardiolipin
Carrying a positive charge, SS-31 crosses membranes and selectively binds cardiolipin. By stabilizing it, it restores the cristae, improves electron transfer, and reduces the production of free radicals by the respiratory chain.
Muscle, heart and retina: the tissues in the trials
The heart, muscles, kidneys, retina and brain use the most energy and contain the most mitochondria. The clinical trials of SS-31 have covered muscle (Barth syndrome, mitochondrial myopathies), the heart (heart failure) and the retina (macular degeneration).
Effects and realistic timelines
Steadier energy, according to users: it binds cardiolipin and preserved the cells' ATP production in the laboratory (Birk, 2013)
According to users: two to four weeks
Muscle strength: the FDA approval of 2025 rests on it
Several months, in the trial that led to the approval
Retina protection: 43% less loss of the ellipsoid zone in the ReCLAIM-2 trial (2025)
Several months
What you may feel
- Reaction at the injection site (redness, itching), the most common effect in the trials.
- Brief headaches or dizziness.
Stop and consult if
- A skin reaction that spreads or persists for more than a few days.
- Unusual palpitations or shortness of breath.
When to abstain
- Pregnancy or breastfeeding.
- A diagnosed mitochondrial or cardiac disease without medical supervision: that calls for a treatment framework, not a wellness one.
- Minors.
The effects to watch for, and how to reduce them
This sheet is educational. It replaces neither a diagnosis nor follow-up: for any medical condition, pregnancy, breastfeeding or current medication, talk to a health professional.
SS-31 has been studied in humans in phase 2 and 3: Barth syndrome, mitochondrial myopathies, heart failure, age-related macular degeneration. Its mechanism on cardiolipin is established and its tolerability well characterized.
Three trials did not meet their primary endpoint: the randomized phase of TAZPOWER, MMPOWER-3 and ReCLAIM-2; the favourable results come from the TAZPOWER open-label extension and from ReCLAIM-2's secondary endpoints.
The 2025 accelerated approval in the United States only covers Barth syndrome, a rare mitochondrial disease, in patients weighing at least 30 kg, and the FDA requires a confirmatory trial.
2013 · Birk et al., Journal of the American Society of Nephrology
Cells and an experimental model of ischemia
SS-31 binds cardiolipin, protects the structure of the mitochondrial cristae, and preserves ATP production during and after an oxygen shortfall.
2004 · Zhao et al., Journal of Biological Chemistry
Isolated mitochondria and cultured cells
The peptide crosses the cell membrane and concentrates about 1,000-fold in the inner mitochondrial membrane, relative to the incubation fluid; there it limits mitochondrial swelling and oxidative cell death.
2021 · Reid Thompson et al., Genetics in Medicine (TAZPOWER trial)
Randomized placebo-controlled crossover trial, 12 patients with Barth syndrome, followed by an open-label extension
During the 12-week randomized phase, neither primary endpoint (6-minute walk test, symptom scale) was met. After 36 weeks of open-label extension, the walk test distance rose by 95.9 m, symptoms improved, and so did the strength of the muscles that straighten the knee: the 2025 accelerated approval rests on that strength.
2023 · Karaa et al., Neurology (MMPOWER-3 trial)
Randomized placebo-controlled phase 3 trial, 218 adults with primary mitochondrial myopathy, 24 weeks
Both primary endpoints, the 6-minute walk test and fatigue, were not met: no difference from placebo. The product was well tolerated, with mostly mild to moderate adverse events. A post hoc analysis published in 2024 looked at effects by genetic profile.
2025 · Ehlers et al., Ophthalmology Science (ReCLAIM-2 trial)
Randomized placebo-controlled phase 2 trial, 176 patients aged 55 and over with dry macular degeneration and geographic atrophy, 48 weeks
The two primary endpoints (low-light visual acuity, atrophy growth) did not reach statistical significance. On predefined endpoints, progression of ellipsoid zone loss was 43% lower than with placebo, and 14.6% of patients gained at least 10 letters in low light, against 2.1% on placebo. The ellipsoid zone becomes the primary endpoint of phase 3.
Are SS-31 and elamipretide the same thing?
Yes: SS-31 is the research name (for Szeto-Schiller, its inventors), elamipretide the drug name. It's the same molecule.
Is it an antioxidant?
Not in the classic sense. An antioxidant neutralizes free radicals once they are produced. SS-31 stabilizes cardiolipin, which improves electron transfer in the respiratory chain and reduces the amount of free radicals it produces.
How long before you feel something?
Two to four weeks for steadier energy, according to user reports. In clinical trials, the measured effects, on muscle strength or the retina, build over several months.
Glossary (5)
- Cardiolipin
- A lipid specific to the mitochondrial inner membrane that organizes the respiratory chain.
- Respiratory chain
- A series of protein complexes that transfer electrons to produce ATP.
- ATP
- Adenosine triphosphate: the molecule that stores and delivers energy in every cell.
- Free radicals
- Unstable molecules produced by metabolism, which damage cellular structures in excess.
- Accelerated approval
- Conditional authorization granted to a drug for a serious disease, based on preliminary results.