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    Fact-checked by the Peptide Authority Editorial Board · Last reviewed:

    Corrected : The MMPOWER-3 summary and FAQ incorrectly said the trial 'showed improvements in some secondary measures'. Per the trial's published Class I conclusion (Karaa et al., Neurology 2023), both co-primary endpoints (6MWT, PMMSA fatigue) failed to reach significance, and because of the pre-specified hierarchical testing plan, secondary endpoints were not formally tested. Text has been rewritten to match the paper.

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    Longevity & Anti-Ageing•Updated 2026-09-25•6 min read

    What Is SS-31? Benefits, Research & Safety

    A mitochondria-targeted tetrapeptide in clinical trials for heart failure, mitochondrial myopathy, and age-related mitochondrial dysfunction.

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    Also known as:
    Elamipretide
    Bendavia
    MTP-131
    D-Arg-Dmt-Lys-Phe-NH2
    CLimited human evidenceUK: Unlicensed (UK)WADA: Sport status unclear

    UK summary: Not a licensed UK medicine. Mitochondria-targeted tetrapeptide (elamipretide / Bendavia) with several human clinical trials in mitochondrial disease and heart failure; not currently licensed for any indication in the UK.

    Quick Facts

    Category
    Longevity & Anti-Ageing
    Half-Life
    Approximately 4 hours (subcutaneous)
    UK Status
    Not licensed. Investigational compound only. Not available on NHS.
    EU Status
    Not approved. May be available through clinical trial participation.

    Overview

    SS-31 (elamipretide) is a synthetic tetrapeptide (D-Arg-2',6'-dimethyltyrosine-Lys-Phe-NH2) that selectively targets and concentrates in the inner mitochondrial membrane. It belongs to the Szeto-Schiller (SS) peptide family, designed to penetrate cell membranes and accumulate in mitochondria. SS-31 binds to cardiolipin, a phospholipid unique to the inner mitochondrial membrane that is essential for the proper function of the electron transport chain. By stabilising cardiolipin and optimising electron transport, SS-31 reduces excessive reactive oxygen species (ROS) production, improves ATP generation, and protects against mitochondrial dysfunction. The peptide has reached clinical trials (Phase II/III) for several conditions including primary mitochondrial myopathy (the MMPOWER trials), heart failure with reduced ejection fraction (the PROGRESS-HF trial), Barth syndrome, and age-related macular degeneration. Results have been mixed—while preclinical data was highly promising, some clinical trials failed to meet primary endpoints. Development continues, with Stealth BioTherapeutics (now Larimar Therapeutics) pursuing various indications. SS-31 represents one of the most advanced mitochondria-targeted therapeutics in development and is of significant interest in ageing research due to the central role of mitochondrial dysfunction in the ageing process.
    Evidence standards summary

    SS-31 — evidence and risk at a glance

    Twenty standard modules scored against the Peptide Authority evidence grading methodology. Missing modules indicate the field has not yet been characterised editorially — treat absences as uncertainty rather than reassurance.

    01Evidence snapshot

    CLimited human evidenceOverall grade against our evidence grading methodology.

    Not a licensed UK medicine. Mitochondria-targeted tetrapeptide (elamipretide / Bendavia) with several human clinical trials in mitochondrial disease and heart failure; not currently licensed for any indication in the UK.

    02Human evidence grade

    ETheoretical / insufficientStrength of evidence from published human trials.

    03Preclinical evidence grade

    BModerate human evidenceAnimal-model and in-vitro evidence quality.

    04Regulatory status

    • UK: Not licensed. Investigational compound only. Not available on NHS.
    • EU: Not approved. May be available through clinical trial participation.
    • Notes: SS-31 (elamipretide) remains investigational. It has FDA Fast Track and Orphan Drug designations for Barth syndrome. Clinical trials continue for various mitochondrial conditions. Not available through standard channels.

    05Approved medical uses

    None in the UK or EU as a finished medicine. (Or: not yet documented; treat as absence rather than approval.)

    06Unapproved / promotional claims

    • Restores mitochondrial function in healthy adults.
    • Treats long COVID and chronic fatigue syndrome.
    • Reverses age-related energy decline.
    • Safe long-term self-administration.

    07Common internet claims

    • Marketed in longevity and chronic-fatigue stacks.
    • Sold by online retailers as research-only injectable.
    • Promoted as 'the most studied mitochondrial peptide' (true within narrow disease indications, not for general health).

    08Claim vs evidence

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Reverses mitochondrial dysfunction in healthy adults”ENoHighTrial evidence is in specific disease populations (e.g. mitochondrial myopathy); generalising to healthy adults is not supported.
    “Approved for heart failure”CYesHighTrials for heart failure / Barth syndrome have produced mixed regulatory outcomes; not a UK-licensed treatment.
    “Safer than other anti-ageing peptides”ENoHighComparative safety claims need comparative trials.

    09Safety uncertainty score

    Moderate

    Safety profile partly characterised; some signals from observational or preclinical data.

    10Known adverse signals

    • Trial use in specific mitochondrial diseases: generally well tolerated.
    • Injection-site reactions.
    • Unknown chronic effects in healthy-adult populations.
    • Failed Phase 3 in Barth syndrome and some heart-failure endpoints — translation outside trial populations uncertain.

    11Drug-interaction uncertainty

    Moderate

    Some interaction data published; check with a prescriber for your specific medicines.

    12Anti-doping status

    WADA: Sport status unclearWADA strict-liability framing applies.

    13UK legal position

    UK: Unlicensed (UK)

    Not licensed. Investigational compound only. Not available on NHS.

    Read the full UK legal guide → Research peptides and UK law

    14EU legal position

    Not approved. May be available through clinical trial participation.

    15What this page cannot tell you

    • Whether a UK-purchased vial contains elamipretide at the labelled concentration.
    • Whether the trial benefit in specific mitochondrial diseases applies to healthy adults or to long COVID.
    • Long-term safety beyond trial endpoints.
    • Whether commercial 'research peptide' SS-31 is the same compound as the clinical-trial elamipretide.

    16Last reviewed

    Last reviewed:

    Next review due:

    Spotted an error or something out of date? Send a correction.

    17Citation quality score

    BModerate human evidenceQuality of the sources we cite, graded against the evidence grading methodology.

    18Research gaps

    • Healthy-adult outcome data absent.
    • Long-COVID and chronic-fatigue RCT evidence absent despite heavy marketing.
    • Long-term safety in non-trial populations unstudied.

    19Safer alternatives / established care pathways

    • Specialist mitochondrial-medicine referral for diagnosed mitochondrial disease.
    • NHS long-COVID clinic referral for post-viral fatigue.
    • Evidence-based fatigue management (pacing, sleep, treatment of comorbid depression/sleep apnoea/anaemia/thyroid).

    Related Safety Centre page → Unlicensed peptide risks

    20Doctor discussion prompts

    Questions to ask a qualified clinician

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is SS-31 / elamipretide a licensed UK medicine?
    • Are there UK clinical trials I might be eligible for?
    • What licensed treatments exist for the underlying mitochondrial concern?

    Discovery & History

    SS-31 was developed by Hazel Szeto and Peter Bhatt Schiller at Weill Cornell Medical College in the early 2000s. The SS peptide series was designed using alternating aromatic-cationic motifs that enable mitochondrial targeting without requiring the typical mitochondrial targeting sequence. The key innovation was the discovery that small, cell-permeable peptides with the right structural features could selectively concentrate in mitochondria at 1,000-5,000 fold higher concentrations than in the cytoplasm. SS-31 was identified as the most promising candidate. Preclinical studies showed remarkable effects: protection against ischaemia-reperfusion injury, reversal of age-related mitochondrial dysfunction in animal models, and improvements in cardiac function. These results generated significant excitement about mitochondria-targeted therapy. Stealth BioTherapeutics was founded to develop SS-31 (as elamipretide) clinically. The company conducted multiple clinical trials across several disease areas. While earlier trials (MMPOWER-1 and -2) showed positive signals in patient-reported outcomes, the pivotal, phase 3 MMPOWER-3 trial in primary mitochondrial myopathy did not meet either of its co-primary endpoints (6-minute walk test or fatigue score); an exploratory post-hoc subgroup analysis found a significant benefit only in the nuclear-DNA disease subgroup. Development continues, with focus on Barth syndrome (which received FDA Fast Track designation) and other mitochondrial conditions.

    Mechanism of Action

    SS-31 targets mitochondria through a unique mechanism: **Cardiolipin Binding** The primary mechanism of action: - Selectively binds to cardiolipin on the inner mitochondrial membrane - Stabilises cardiolipin's interaction with cytochrome c - Prevents cardiolipin peroxidation - Maintains proper cristae structure **Electron Transport Chain Optimisation** Improves mitochondrial bioenergetics: - Enhances Complex I-IV function - Reduces electron leak and excessive ROS production - Improves coupling efficiency between complexes - Increases ATP production per oxygen consumed **ROS Reduction** Reduces oxidative damage without acting as a scavenger: - Prevents excess ROS generation at the source - Does not interfere with physiological ROS signaling - Protects mitochondrial proteins and lipids from oxidative damage - Reduces mitochondrial DNA damage **Mitochondrial Membrane Potential** Maintains proper membrane function: - Stabilises mitochondrial membrane potential - Prevents permeability transition pore opening - Reduces cytochrome c release - Inhibits apoptosis triggered by mitochondrial dysfunction

    Researched Benefits

    Based on preclinical and clinical research findings:

    • 1
      Improved mitochondrial function and ATP production
    • 2
      Reduced mitochondrial ROS production
    • 3
      Cardioprotection in ischaemia-reperfusion models
    • 4
      Reversal of age-related mitochondrial decline (animal studies)
    • 5
      Potential benefits in heart failure (clinical trials ongoing)
    • 6
      Improved exercise capacity in mitochondrial myopathy patients
    • 7
      Renal protection in acute kidney injury models

    Claim vs Evidence

    How popular claims about SS-31 stack up against the current research, graded using our public evidence grading methodology.

    ClaimEvidenceHuman evidence?Regulatory concernSafer wording
    “Reverses mitochondrial dysfunction in healthy adults”ENoHighTrial evidence is in specific disease populations (e.g. mitochondrial myopathy); generalising to healthy adults is not supported.
    “Approved for heart failure”CYesHighTrials for heart failure / Barth syndrome have produced mixed regulatory outcomes; not a UK-licensed treatment.
    “Safer than other anti-ageing peptides”ENoHighComparative safety claims need comparative trials.

    Theoretical Dosing & Protocols

    ⚠️ Educational Only: The following information is derived from research literature and is not a prescription or recommendation. No standardised human dosing exists. Always consult a qualified healthcare professional.
    Theoretical DosageClinical trials have used 4-40 mg subcutaneous or IV
    FrequencyDaily subcutaneous injection in most trials
    DurationClinical trials ranged from 4 weeks to 6 months
    NotesSS-31/elamipretide is an investigational drug. It is not approved for any indication. Use outside of clinical trials is not recommended. Results from clinical trials have been mixed.

    Administration Routes

    Routes studied in research settings (educational only):

    • Subcutaneous injection (primary clinical route)
    • Intravenous infusion (some trial protocols)
    Half-LifeStability
    Approximately 4 hours (subcutaneous)Lyophilised powder stored at controlled temperatures; reconstituted solution used promptly

    Safety Profile & Known Risks

    Commonly Reported Side Effects

    • Injection site reactions
    • Headache
    • Nausea
    • Fatigue

    Rare Risks & Concerns

    • QTc prolongation (observed at high doses in some studies)
    • Renal effects at very high doses
    • Limited long-term safety data

    Contraindications

    • Not approved for human use outside clinical trials
    • Known hypersensitivity to SS-31
    • Pregnancy and breastfeeding
    • Significant renal impairment (dose adjustment may be needed)

    UK & EU Regulatory Context

    🇬🇧 United Kingdom

    Not licensed. Investigational compound only. Not available on NHS.

    🇪🇺 European Union

    Not approved. May be available through clinical trial participation.

    SS-31 (elamipretide) remains investigational. It has FDA Fast Track and Orphan Drug designations for Barth syndrome. Clinical trials continue for various mitochondrial conditions. Not available through standard channels.

    Clinical Studies Summary

    MMPOWER-3 Trial for Mitochondrial Myopathy

    Phase III trial (n=218) of elamipretide 40 mg/day subcutaneously for 24 weeks in primary mitochondrial myopathy. Both co-primary endpoints failed: the between-group difference was -3.2 metres on the 6-minute walk test (p=0.69) and -0.07 on the PMMSA fatigue score (p=0.37). Because the primary endpoints were not met, the pre-specified hierarchical plan meant secondary endpoints were not formally tested. The authors concluded this provides Class I evidence that elamipretide does not improve the 6MWT or fatigue at 24 weeks versus placebo.

    Neurology. 2023View on PubMed

    Therapeutic Approaches Involving Mitochondria in the Treatment of Acute Kidney Injury.

    Concerns regarding cost, accessibility, and long-term safety remain unresolved, contributing to inconsistent outcomes in clinical trials. Herein we evaluate the emerging role of PLSCR3 as a potentially druggable mitochondrial target, supported by recent genetic, biochemical, and in vivo evidence, and discuss translational strategies that may bridge the gap between experimental promise and clinical application.

    Semin Nephrol. 2026View on PubMed

    Mitochondrial Metabolic Checkpoints in Human Fertility: Reactive Oxygen Species as Gatekeepers of Gamete Competence.

    Understanding ROS-mediated checkpoints forms the basis for developing biomarkers of gamete competence and precision therapies to improve ART outcomes. By highlighting mitochondria as both metabolic sensors and redox regulators, this review links fundamental mitochondrial biology to clinical reproductive medicine.

    Cells. 2026View on PubMed

    Drug repurposing in Alzheimer's disease: Emerging therapeutic strategies and promising candidates.

    The development of artificial intelligence, multi-omics, and precision medicine also improves drug repurposing plans. Overall possibility to integrate multi-target repurposed therapies with novel technologies is a promising prospect to overcome the available shortcomings and improve clinical outcomes in AD.

    Ageing Res Rev. 2026View on PubMed

    The Potential of Mitochondrial Therapeutics in the Treatment of Oxidative Stress and Inflammation in Aging.

    Consent to Participate: Not applicable. Consent for Publication: Not applicable.

    Mol Neurobiol. 2025View on PubMed

    Innovative technologies for the treatment of dry age-related macular degeneration (AMD) - modern therapeutic perspectives and their future.

    Modern therapeutic approaches for dry AMD provide promising avenues to slow disease progression and protect vision. However, further clinical trials are needed to optimize these strategies, assess long-term outcomes, and expand patient access to effective treatments. These advancements have the potential to significantly improve the quality of life for individuals affected by dry AMD.

    Rom J Ophthalmol. 2025View on PubMed

    Registered Trials & Regulatory Status

    Registered trials
    30
    Currently recruiting
    2
    Furthest phase
    Phase 4
    Approved product
    No

    11 of 22 completed trials have never posted results. Unreported trials are not neutral: results that go unpublished are more often negative ones.

    Clinical Trial in Patients With Barth Syndrome- 4TAZPower

    PHASE4

    Status: Recruiting · 48 participants · Stealth BioTherapeutics Inc.

    Conditions: Barth Syndrome

    No results postedNCT07531251

    Study of Healthy Aging and Physical Function With Elamipretide

    PHASE2

    Status: Recruiting · 30 participants · David Marcinek

    Conditions: Aging, Healthy

    No results postedNCT07275424

    ReNEW:Phase 3 Study of Efficacy, Safety & Pharmacokinetics of Subcutaneous Injections of Elamipretide in Subjects With Dry Age-Related Macular Degeneration (Dry AMD)

    PHASE3

    Status: Active Not Recruiting · 313 participants · Stealth BioTherapeutics Inc.

    Conditions: Age Related Macular Degeneration (ARMD)

    No results postedNCT06373731

    Study to Evaluate Efficacy and Safety of Elamipretide in Subjects With Primary Mitochondrial Disease From Nuclear DNA Mutations (nPMD)

    PHASE3

    Status: Completed · 102 participants · Stealth BioTherapeutics Inc.

    Conditions: Mitochondrial Myopathies, Mitochondrial Pathology, Mitochondrial DNA Mutation

    No results postedNCT05162768

    FRDA Investigator Initiated Study (IIS) With Elamipretide

    PHASE1/PHASE2

    Status: Completed · 20 participants · Children's Hospital of Philadelphia

    Conditions: Friedreich Ataxia

    Results postedNCT05168774

    ReCLAIM-2 Study to Evaluate Safety,Efficacy & Pharmacokinetics of Elamipretide in Subjects With AMD With Non-central GA

    PHASE2

    Status: Completed · 176 participants · Stealth BioTherapeutics Inc.

    Conditions: Age-related Macular Degeneration

    Results postedNCT03891875

    A Trial to Evaluate Safety and Efficacy of Elamipretide Primary Mitochondrial Myopathy Followed by Open-Label Extension

    PHASE3

    Status: Terminated · 218 participants · Stealth BioTherapeutics Inc.

    Conditions: Primary Mitochondrial Myopathy

    Results postedNCT03323749

    A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects With Barth Syndrome

    PHASE2/PHASE3

    Status: Completed · 12 participants · Stealth BioTherapeutics Inc.

    Conditions: Barth Syndrome

    Results postedNCT03098797

    Open-Label Extension Trial to Characterize the Long-term Safety and Tolerability of Elamipretide in Subjects With Genetically Confirmed Primary Mitochondrial Myopathy (PMM)

    PHASE2

    Status: Terminated · 28 participants · Stealth BioTherapeutics Inc.

    Conditions: Primary Mitochondrial Disease

    Results postedNCT02976038

    An Open-Label, Phase 1 Clinical Study to Evaluate the Safety and Tolerability of Subcutaneous Elamipretide in Subjects With Intermediate Age-Related Macular Degeneration

    PHASE1

    Status: Completed · 40 participants · Stealth BioTherapeutics Inc.

    Conditions: Age-Related Macular Degeneration

    Results postedNCT02848313

    A Phase 2 Study to Evaluate the Cardiac and Renal Effects of Short Term Treatment With Elamipretide in Patients Hospitalized With Congestion Due to Heart Failure

    PHASE2

    Status: Completed · 308 participants · Stealth BioTherapeutics Inc.

    Conditions: Heart Failure

    No results postedNCT02914665

    A Study to Evaluate the Effects of 4 Weeks Treatment With Subcutaneous Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Preserved Ejection Fraction

    PHASE2

    Status: Completed · 46 participants · Stealth BioTherapeutics Inc.

    Conditions: Chronic Heart Failure

    No results postedNCT02814097

    Adverse event reports (FDA FAERS)

    Not applicable: no licensed product contains this peptide, so it is not reported through FAERS. This is an absence of surveillance, not evidence of safety.

    Source: ClinicalTrials.gov and openFDA. Updated automatically.

    Looking for SS-31?

    Source research-grade SS-31 from a trusted UK supplier — third-party tested with certificate of analysis.

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    Frequently Asked Questions

    Questions to ask a qualified clinician about SS-31

    These are starter questions you can adapt for a GP, specialist, pharmacist, or anti-doping advisor. The aim is to help you have a better-informed conversation — not to replace one.

    • Is SS-31 / elamipretide a licensed UK medicine?
    • Are there UK clinical trials I might be eligible for?
    • What licensed treatments exist for the underlying mitochondrial concern?

    UK regulatory & safety context

    Research peptides and UK law

    UK legal reference

    Unlicensed peptide risks

    Safety Centre guide

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