SS-31
Published research and evidence base
Elamipretide (SS-31, MTP-131) is a mitochondria-targeted tetrapeptide that binds cardiolipin in the inner mitochondrial membrane, stabilising cristae architecture and improving electron transport efficiency and ATP synthesis. It has been studied in randomised controlled trials in Barth syndrome, primary mitochondrial myopathy, heart failure with reduced ejection fraction, Leber hereditary optic neuropathy and ischaemia-reperfusion settings, with mixed results: the Barth syndrome programme showed sustained functional gains in a small cohort, while the phase 3 MMPOWER-3 trial in primary mitochondrial myopathy missed its primary endpoints. On 19 September 2025 the FDA granted accelerated approval to elamipretide (FORZINITY, NDA 215244, Stealth BioTherapeutics) to improve muscle strength in adult and paediatric patients with Barth syndrome weighing at least 30 kg, based on an improvement in knee extensor muscle strength; continued approval is contingent on confirmatory trials. Evidence for use in healthy individuals or for athletic performance is absent.
- Studies cited
- 16
- Published 2023+
- 11
- Newest paper
- 2026
- Last reviewed
- Aug 2026
Recurring themes in the literature
- cardiolipin binding
- mitochondrial cristae stabilisation
- ATP synthesis and bioenergetics
- Barth syndrome
- primary mitochondrial myopathy
- heart failure and cardiac bioenergetics
- six-minute walk test
- ischaemia-reperfusion injury
- skeletal muscle fatigue
- mitochondria-targeted tetrapeptide
Compound identifiers
- CAS
- 736992-21-5
- PubChem
- 11764719
What SS-31 is, chemically.
- Molecular formula
- C32H49N9O5
- Molecular weight
- 639.8 g/mol
- CAS number
- 736992-21-5
- PubChem CID
- 11764719
Elamipretide, bendavia, Ocuvia
These figures come from the PubChem record for this compound and describe the free base. Lyophilised peptide is normally supplied as an acetate or trifluoroacetate salt and carries residual water, so the mass of powder in a vial is not the same quantity as the molecular weight above would suggest. Chromatographic purity on a certificate of analysis does not resolve that difference either — how to read a certificate of analysis explains why.
16 published studies.
Ordered by strength of study design, then by recency. Every entry links to its source record so the finding can be checked against the paper rather than taken on our word.
- 01Human clinical2026
Elamipretide in pediatric Barth syndrome: from heart failure to school return
Amedro P, et al. · Orphanet Journal of Rare Diseases · Single-patient compassionate-use case report; 5-year-old with genetically confirmed Barth syndrome and severe heart failure
Left ventricular ejection fraction rose from 20% to 50% during compassionate-use elamipretide, the child returned to full-time school and was temporarily suspended from the transplant list. As a single case report this cannot establish efficacy.
- 02Human clinical2025
Initial Psychometric Evaluation of the Barth Syndrome Symptom Assessment (BTHS-SA) for Adolescents and Adults in a Phase 2 Clinical Study
Gwaltney C, et al. · Orphanet Journal of Rare Diseases · Psychometric analysis nested in a phase 2 randomised, double-blind, placebo-controlled crossover elamipretide study; 12 male patients with Barth syndrome
The Barth Syndrome Symptom Assessment produced reliable scores in this cohort, supporting its use as a patient-reported outcome measure in elamipretide trials.
- 03Human clinical2024
Long-term efficacy and safety of elamipretide in patients with Barth syndrome: 168-week open-label extension results of TAZPOWER
Thompson WR, et al. · Genetics in Medicine · 168-week open-label extension of the TAZPOWER randomised crossover trial; 10 patients with genetically confirmed Barth syndrome entered, 8 reached week 168; elamipretide 40 mg subcutaneous daily
Cumulative six-minute walk distance improved by 96.1 m at week 168 relative to open-label extension baseline (P = .003), with improvements also reported in fatigue scores and cardiac function measures. Injection-site reactions were the most common adverse event.
- 04Human clinical2024
Genotype-specific effects of elamipretide in patients with primary mitochondrial myopathy: a post hoc analysis of the MMPOWER-3 trial
Karaa A, et al. · Orphanet Journal of Rare Diseases · Post hoc genotype-stratified analysis of the phase 3 randomised, double-blind, placebo-controlled MMPOWER-3 trial in primary mitochondrial myopathy
Participants with mtDNA replisome disorders and those with chronic progressive external ophthalmoplegia showed improvement on the six-minute walk test with elamipretide, whereas the overall trial population did not.
- 05Human clinical2024
Elamipretide Topical Ophthalmic Solution for the Treatment of Subjects with Leber Hereditary Optic Neuropathy: A Randomized Trial
Karanjia R, et al. · Ophthalmology · Phase 2 prospective randomised, double-masked, vehicle-controlled trial; 12 subjects with Leber hereditary optic neuropathy, 52 weeks of topical ophthalmic elamipretide
The trial did not meet its primary best-corrected visual acuity endpoint; a post hoc analysis reported improvement in central visual field mean deviation.
- 06Human clinical2023
Efficacy and Safety of Elamipretide in Individuals With Primary Mitochondrial Myopathy: The MMPOWER-3 Randomized Clinical Trial
Karaa A, et al. · Neurology · Phase 3 randomised, double-blind, placebo-controlled trial; 218 participants with primary mitochondrial myopathy (109 elamipretide, 109 placebo), 24 weeks
Elamipretide did not meet the primary endpoints of change in six-minute walk test distance or fatigue score compared with placebo. The drug was generally well tolerated.
- 07Human clinical2023
Identifying responders to elamipretide in Barth syndrome: Hierarchical clustering for time series data
Van den Eynde J, et al. · Orphanet Journal of Rare Diseases · Secondary clustering analysis of the randomised, double-blind, placebo-controlled crossover TAZPOWER trial; 12 patients with Barth syndrome
Agglomerative hierarchical clustering of longitudinal outcome data separated treatment responders from non-responders within the trial cohort, indicating heterogeneous individual response to elamipretide.
- 08Human clinical2021
A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism
Reid Thompson W, et al. · Genetics in Medicine · Phase 2/3 randomised, double-blind, placebo-controlled crossover trial with open-label extension (TAZPOWER); 12 subjects with Barth syndrome
The randomised crossover phase did not show a significant difference on primary endpoints, but at 36 weeks of open-label treatment six-minute walk distance improved by 95.9 m and the Barth Syndrome Symptom Assessment total fatigue score improved by 2.1 points.
- 09Human clinical2021
In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial
Roshanravan B, et al. · PLoS One · Randomised, double-blind, placebo-controlled single-dose study; 39 healthy older adults, phosphorus magnetic resonance spectroscopy of skeletal muscle
A single infusion of elamipretide raised in vivo skeletal muscle mitochondrial energetic capacity relative to placebo immediately after infusion. The study measured a short-term bioenergetic endpoint, not exercise performance.
- 10Human clinical2020
A randomized crossover trial of elamipretide in adults with primary mitochondrial myopathy
Karaa A, et al. · Journal of Cachexia, Sarcopenia and Muscle · Randomised, double-blind, placebo-controlled crossover trial (MMPOWER-2); 30 adults with primary mitochondrial myopathy, 4-week treatment periods
Participants receiving elamipretide reported less fatigue and fewer muscle complaints than on placebo, though objective functional endpoints were not consistently improved.
- 11Human clinical2020
Effects of Elamipretide on Left Ventricular Function in Patients With Heart Failure With Reduced Ejection Fraction: The PROGRESS-HF Phase 2 Trial
Butler J, et al. · Journal of Cardiac Failure · Phase 2 randomised, double-blind, placebo-controlled trial; 71 patients with heart failure with reduced ejection fraction, 4 weeks
Elamipretide was well tolerated but did not improve left ventricular end-systolic volume at 4 weeks compared with placebo.
- 12Animal in vivo2026
Targeting Mitochondrial Dysfunction With Elamipretide (SS-31) Improves Skeletal Muscle Performance in a HFpEF Rat Model
Vahle B, et al. · Circulation: Heart Failure · Female Zucker fatty spontaneously hypertensive rats, a model of heart failure with preserved ejection fraction
In this rat model elamipretide improved whole-muscle contractile function by 8.2-10.9% and prevented fibre atrophy, with the authors attributing the effect to cardiolipin stabilisation. These findings are animal data and have not been reproduced in humans.
- 13Animal in vivo2026
Mitochondrial Targeting by Elamipretide Improves Myocardial Bioenergetics Without Translating into Functional Benefits in HFpEF
Schauer A, et al. · International Journal of Molecular Sciences · Female obese ZSF1 rats with heart failure with preserved ejection fraction
Despite modest improvements in mitochondrial respiration, diastolic dysfunction persisted and no structural or functional cardiac benefit was observed in these rats.
- 14Animal in vivo2026
Elamipretide Improves Mitochondrial Function in Mitochondrial Trifunctional Protein-Deficient Mice and Human Fibroblasts
Vieira Neto E, et al. · Journal of Inherited Metabolic Disease · Mitochondrial trifunctional protein beta-subunit deficient mice plus patient-derived human fibroblasts
Elamipretide increased exercise endurance in the deficient mice and improved bioenergetics in patient fibroblasts, with the effect apparently independent of changes in cardiolipin content. These are animal and cell findings only.
- 15Animal in vivo2013
The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin
Birk AV, et al. · Journal of the American Society of Nephrology · Rat kidney ischaemia-reperfusion model with accompanying isolated mitochondria mechanistic work
SS-31 was shown to bind cardiolipin, protect cristae architecture, restore ATP production and reduce acute kidney injury in this model. This is the foundational paper establishing the cardiolipin mechanism.
- 16Review2026
Elamipretide: a mitochondria-targeting drug for Barth syndrome
Villatore A, et al. · Trends in Pharmacological Sciences · Narrative review of elamipretide pharmacology in Barth syndrome following its regulatory approval
The review summarised how elamipretide stabilises cardiolipin and improves mitochondrial function in Barth syndrome, an X-linked disorder of cardiolipin remodelling.
What this evidence does not establish.
Elamipretide's only approved indication is Barth syndrome, granted under accelerated approval on a muscle-strength surrogate endpoint in a very small cohort, and confirmatory clinical benefit has not yet been demonstrated; the largest randomised trial in primary mitochondrial myopathy (MMPOWER-3, n=218) missed its primary endpoints, as did the phase 2 heart failure and Leber hereditary optic neuropathy trials. There are no controlled trials of elamipretide in healthy individuals for exercise capacity, athletic performance, longevity or body composition, and long-term safety data outside the small Barth syndrome cohorts are limited.
Common questions about the research.
- What is SS-31?
SS-31, also called elamipretide, is a mitochondria-targeted tetrapeptide from the Szeto-Schiller series. It concentrates in the inner mitochondrial membrane and binds the phospholipid cardiolipin, and it is one of the more clinically advanced investigational compounds in mitochondrial research.
- Is SS-31 an antioxidant?
It was originally characterised that way, but the mechanism described in the current literature is more specific. Rather than scavenging free radicals in bulk, the peptide binds cardiolipin, stabilises cristae curvature, and prevents cardiolipin-bound cytochrome c from acquiring peroxidase activity — reduced oxidative stress follows from the structural interaction rather than from direct scavenging.
- How does SS-31 differ from NAD+ in mitochondrial research?
They address different layers of the same system. SS-31 acts on the physical architecture of the inner membrane through cardiolipin binding, whereas NAD+ work concerns the redox cofactor pool that feeds the electron transport chain and the NAD+-consuming enzymes. The two are frequently discussed side by side in mitochondrial-ageing reviews.
Available from our catalog
For research purposes only. Not for human consumption, diagnosis, treatment, or prevention of any condition. Nothing on this page is medical advice, and no study summarised here should be read as a recommendation.