SS-31

SS-31 (elamipretide) is a mitochondria-targeting peptide best known for supporting cellular energy and reducing oxidative stress. It works by stabilizing cardiolipin — a fat that holds together the inner membrane of the cell's 'power plants' (mitochondria) — so they run cleaner. In 2025 it became the first FDA-approved treatment for a mitochondrial disease (Barth syndrome); its broader energy, recovery, and longevity uses are off-label and haven't been proven in large human trials. Taken as a small injection under the skin.

SS-31 (elamipretide) is a mitochondria-targeting peptide, FDA-approved for the rare condition Barth syndrome and studied off-label for broader mitochondrial and recovery uses. In the pivotal TAZPOWER trial (a small Phase 2/3 study with an open-label extension), it was associated with improvements in a 6-minute walk test, cardiac stroke volume, and a cardiolipin biomarker in Barth syndrome. The broader off-label uses (general mitochondrial dysfunction, longevity, recovery) have not been validated in large trials, and several Phase 3 trials in other conditions did not meet their goals.

FDA-approved September 19, 2025 under FDA Accelerated Approval as FORZINITY (elamipretide) to improve muscle strength in Barth syndrome in adults and pediatric patients weighing at least 30 kg — the first FDA-approved therapy for any mitochondrial disease. Approval pathway is Accelerated Approval (intermediate endpoint = knee-extensor muscle strength), with a confirmatory trial required to verify clinical benefit; that confirmatory study — 4TAZPower (NCT07531251), Phase 3b/4 — is now enrolling (recruiting; started July 2026). Manufacturer: Stealth BioTherapeutics. Outside the FDA-approved Barth syndrome indication, all use is off-label. Available in research-community contexts as a research peptide for off-label longevity, fatigue, and recovery indications. Not currently listed in the WADA 2026 Prohibited List (the compound's mechanism is mitochondrial-membrane stabilization rather than anabolic or performance-enhancing in the WADA sense; researchers competing in WADA-tested sport should still confirm against the most recent edition before any competitive event given the recent FDA approval).

SS-31 (FORZINITY) is FDA-approved only for Barth syndrome under Accelerated Approval; all other uses are off-label and not validated by trials. It is not currently listed on the WADA Prohibited List. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. SS-31 (elamipretide, brand name FORZINITY) is FDA-approved as of September 2025 for Barth syndrome but all other uses are off-label. Information in this entry is informational, not medical advice. Always confirm dose calculations and consult appropriate professional guidance before any protocol decisions, particularly for off-label use which lacks FDA-approval-grade clinical guidance.

⚠️ First-in-class FDA-approved mitochondrial therapy. SS-31's FDA Accelerated Approval on September 19, 2025 for Barth syndrome makes elamipretide the first FDA-approved therapy for any mitochondrial disease. The approval pathway is Accelerated Approval, which means the FDA accepted surrogate endpoints (cardiolipin biomarker improvements, 6-minute walk test improvements, cardiac stroke volume) as supporting clinical benefit, with confirmatory trial(s) required to verify the surrogate-to-clinical-benefit translation. The pivotal evidence base for the approval is the TAZPOWER trial (Phase 2/3, n=12 in original phase + open-label extension), conducted at Johns Hopkins and other sites, with results published in 2021.[¹]

⚠️ Off-label research-community use is supported by mechanism but not by RCT-grade efficacy data for non-Barth indications. Despite the FDA approval for Barth syndrome, the broader off-label use cases popular in the research-community (general mitochondrial dysfunction, longevity, fatigue, age-related decline, recovery from physical training) have not been validated in published large-scale RCTs at the doses or durations used in research-community protocols. Stealth BioTherapeutics' multi-indication program spans heart failure (Phase 2), primary mitochondrial myopathy (Phase 3 — the MMPOWER-3 trial, which missed its 6-minute walk distance primary endpoint and is the pathway behind the elamipretide Complete Response Letter), and dry age-related macular degeneration / geographic atrophy (Phase 3 — the ReNEW trial, NCT06373731, still ongoing with results not yet reported) — none of these has produced an approval. The FDA approval is specifically for Barth syndrome based on the TAZPOWER evidence, not for the broader off-label uses. Researchers should be explicit with themselves about what is and is not supported by the FDA approval.

⚠️ Precision matters at low doses. SS-31 is dosed in milligrams per dose (typical range subcutaneous in research-community use; is the FDA-approved Barth syndrome dose), but at typical reconstitution concentrations the draws still land in the small-volume range on a U-100 syringe. Always verify draws against the in-app calculator and double-check the unit count on the syringe before injecting.

⚠️ Mechanism — cardiolipin stabilization at the inner mitochondrial membrane. SS-31 is a 4-amino-acid cell-penetrating peptide (sequence d-Arg-2',6'-Dmt-Lys-Phe-NH2 — incorporating non-standard residues including D-arginine and 2',6'-dimethyltyrosine) that selectively targets and binds cardiolipin, the unique phospholipid concentrated in the inner mitochondrial membrane.[¹] By stabilizing cardiolipin, SS-31 supports the proper organization of electron transport chain complexes, ATP synthase function, and mitochondrial cristae architecture. In Barth syndrome, the TAFAZZIN gene mutation produces abnormal cardiolipin remodeling, causing mitochondrial dysfunction across cardiac, skeletal muscle, and immune tissues — SS-31 partially compensates for the defective cardiolipin maturation. The mechanism is mitochondrial-membrane-stabilizing rather than direct ATP-production-enhancing; downstream effects on energy metabolism, oxidative stress, and cellular function follow from the membrane-stabilization upstream effect.

SS-31 (elamipretide; also Bendavia, MTP-131; FDA-approved brand name FORZINITY) is a synthetic tetrapeptide developed by Stealth BioTherapeutics (originally Stealth Peptides), a US-based biotechnology company spun out from research conducted in Hazel Szeto's laboratory at Cornell Medical College. The "SS" prefix refers to the original Szeto-Schiller laboratory designation; subsequent development was led by Stealth BioTherapeutics across approximately two decades of clinical trials in multiple indications. The compound was the first member of a class of mitochondrial-targeted peptides (the "SS peptides") characterized by cardiolipin binding and inner-membrane stabilization.

FDA Accelerated Approval — September 19, 2025. After approximately a decade of clinical development across multiple indications (heart failure, primary mitochondrial myopathy, dry age-related macular degeneration / geographic atrophy, Barth syndrome), Stealth BioTherapeutics received FDA Accelerated Approval for elamipretide on September 19, 2025, under the brand name FORZINITY, to improve muscle strength in Barth syndrome in adults and pediatric patients weighing at least 30 kg (the accelerated-approval intermediate endpoint was knee-extensor muscle strength).[³] This is the first FDA-approved therapy for any mitochondrial disease[⁵] — a regulatory milestone that took years and a Complete Response Letter (in the primary-mitochondrial-myopathy pathway) to achieve. The Accelerated Approval pathway is based on surrogate/intermediate endpoints (muscle strength, cardiolipin biomarker improvements, 6-minute walk test, cardiac stroke volume); a confirmatory trial is required to verify the clinical benefit translation. That confirmatory study — 4TAZPower (NCT07531251), a Phase 3b/4 randomized, double-blind, placebo-controlled trial with knee-extensor muscle strength as its intermediate endpoint — is now recruiting (started July 2026).

TAZPOWER trial — the pivotal evidence base. The pivotal evidence supporting the FDA approval is the TAZPOWER trial, a Phase 2/3 randomized, double-blind, placebo-controlled clinical trial at Johns Hopkins Hospital and other sites, followed by a longer-term open-label extension. The original 28-week phase enrolled 12 patients with Barth syndrome and was followed by an open-label extension that continued through 2021. In the extension, patients improved on average 95.9 meters per person on the 6-minute walk test compared with baseline (the figure reported in the TAZPOWER publication). Cardiac stroke volume improved. Cardiolipin levels improved compared with study initiation. Patients reported reduced fatigue.[¹] An FDA advisory committee in October 2024 voted that elamipretide was effective for the treatment of Barth syndrome, leading to the Accelerated Approval in September 2025.

Mechanism — cardiolipin stabilization in detail. Cardiolipin is a unique double-glycerolipid concentrated in the inner mitochondrial membrane (~20% of inner membrane phospholipid by mass). It plays multiple structural and functional roles: organizing the electron transport chain complexes into supercomplexes, supporting ATP synthase function, maintaining cristae architecture, and providing a localization platform for apoptosis-regulating proteins. SS-31 selectively binds cardiolipin via electrostatic and hydrophobic interactions, stabilizing the membrane organization and supporting normal mitochondrial function.[⁶] In Barth syndrome, the TAFAZZIN gene mutation produces a defective acyltransferase enzyme responsible for cardiolipin remodeling, leading to abnormal "monolyso-cardiolipin" accumulation and reduced mature tetra-acyl cardiolipin — SS-31 partially compensates by stabilizing whatever mature cardiolipin remains and supporting mitochondrial function despite the underlying defect. In other mitochondrial dysfunction contexts (aging, oxidative stress, ischemia-reperfusion injury), the mechanism logic extends but the clinical translation has been less successful in published Phase 3 trials.

Common research interests (off-label). SS-31's research-community use spans: - General mitochondrial dysfunction — fatigue, age-related cognitive decline, exercise intolerance attributed to "mitochondrial inefficiency". The mechanistic rationale extrapolates from the Barth syndrome data; the clinical evidence for these uses is not RCT-grade. - Longevity / "anti-aging" protocols — research-community use as a mitochondrial-support intervention in longevity stacks. Not RCT-validated. - Recovery from physical training and overtraining — research-community use on the rationale that mitochondrial cardiolipin damage occurs during intense exercise and SS-31 supports recovery. Mechanistically plausible but not RCT-validated. - Heart failure with reduced ejection fraction (HFrEF) — historical Phase 2 evidence base, ultimately did not achieve approval. Off-label research-community use persists. - Geographic atrophy of the macula / dry AMD — under active investigation: the Phase 3 ReNEW trial (NCT06373731) is ongoing, with results not yet reported. This indication has not produced a Complete Response Letter — the CRL sits in the primary-mitochondrial-myopathy pathway (see below).

Regulatory status — multi-indication context. Beyond the Barth syndrome approval, Stealth BioTherapeutics' program has spanned heart failure (Phase 2), primary mitochondrial myopathy (Phase 3 — the MMPOWER-3 trial, NCT03323749, missed its 6-minute walk distance primary endpoint, and this pathway is the one behind the elamipretide NDA's Complete Response Letter and subsequent accelerated-approval resubmission), and dry age-related macular degeneration / geographic atrophy (Phase 3 — the ReNEW trial, NCT06373731, is ongoing with results not yet reported). The current FDA approval is specifically for Barth syndrome under Accelerated Approval; other indications remain investigational or have been discontinued. SS-31 is not currently listed in the WADA 2026 Prohibited List[⁴] — direct text-search of the canonical 2026 WADA pdf returned no matches for "SS-31", "elamipretide", "FORZINITY", or "Bendavia". The compound's mechanism (mitochondrial-membrane stabilization) is not anabolic or performance-enhancing in the WADA-listed sense; however, given the FDA approval is recent (September 2025), researchers competing in WADA-tested sport should confirm against the most recent annual Prohibited List edition before any competitive event — WADA may add elamipretide in future editions if performance-enhancing potential is established.

Commonly reported

• Injection site reactions (common; typically mild local redness, swelling, or pain at the injection site)
• Headache
• Fatigue
• Dizziness
• Nausea
• No serious treatment-related adverse events reported as causally related to elamipretide in the Barth syndrome program
• Injection site reactions (consistent with the trial data)
• Mild GI symptoms (uncommon)
• Occasional headache
• No consistent pattern of serious adverse events in research-community reports
• Long-term safety beyond ~5-year courses — the longest cumulative exposure in the published clinical literature is the TAZPOWER open-label extension; longer-term safety surveillance will accumulate as the FDA-approved product enters broader use.
• Drug interactions — limited characterization of drug-drug interactions in non-Barth populations.
• Pregnancy and lactation safety — limited data; FORZINITY labeling will specify the official pregnancy/lactation guidance.

Pregnancy and lactation — refer to FORZINITY prescribing information for the FDA-approved Barth indication; default to caution for off-label uses.

Pediatric use under 30 kg — FDA approval specifies ≥30 kg; below that weight is off-label.

Active major hepatic or renal impairment — limited characterization of pharmacokinetics; caution.

Known peptide allergy or hypersensitivity — contraindicated.

Regulatory note (US): Elamipretide (FORZINITY) is FDA-approved (September 2025) for Barth syndrome. All other uses are off-label.

Regulatory note (WADA): SS-31 / elamipretide is not currently listed in the 2026 WADA Prohibited List.[⁴] Given the recent FDA approval, future WADA editions may evaluate elamipretide for inclusion; researchers competing in WADA-tested sport should confirm against the most recent annual Prohibited List edition before any competitive event.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Mitochondrial peptide

A peptide whose action centers on mitochondria, the cell's energy- producing structures.

Cardiolipin

A phospholipid concentrated in the inner mitochondrial membrane that helps organize the cell's energy-producing machinery.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Off-label

Use of an approved drug for a purpose, dose, or group not specified on its FDA label.

1. Reid Thompson W, Hornby B, Manuel R, Bradley E, Laux J, Carr J, Vernon HJ. (2021). 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. Genetics in Medicine, 23(3):471-478. doi: 10.1038/s41436-020-01006-8.(PMID 33077895)
2. Szeto HH. (2014). First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. British Journal of Pharmacology, 171(8):2029-2050. doi: 10.1111/bph.12461.(PMID 24117165)
3. US Food and Drug Administration. FORZINITY (elamipretide hydrochloride) Prescribing Information. New Drug Application (NDA) 215244, sponsor Stealth BioTherapeutics. FDA Accelerated Approval September 19, 2025 as ORIG-1, Type 1 (New Molecular Entity), Priority Review with Orphan Drug designation, for Barth syndrome in adults and pediatric patients weighing ≥30 kg. Single-strength formulation: solution containing elamipretide base per 3.5 mL vial, subcutaneous route. The FDA primary regulatory citation for FORZINITY (elamipretide) — first FDA-approved therapy for any mitochondrial disease. Cited in the Status, About, Dosing Protocol, and Regulatory note sections. FDA
4. World Anti-Doping Agency. The 2026 Prohibited List, International Standard (effective 1 January 2026). Canonical PDF: wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf (local archival copy in `docs/legal/wada-2026-prohibited-list.pdf`). SS-31 / elamipretide is not listed in the 2026 WADA Prohibited List.
5. Elamipretide: a mitochondria-targeting drug for Barth syndrome. Trends in Pharmacological Sciences, July 2026. doi: 10.1016/j.tips.2026.06.011.(PMID 42448476)
6. Cardiolipin remodelling in mitochondrial therapeutics: translational evidence chains from elamipretide to emerging strategies. Frontiers in Physiology, May 2026. doi: 10.3389/fphys.2026.1813119.(PMID 42291734 · NCT07531251)

• MOTS-c — discussed together in this entry's stacks section
• Humanin — same mechanism class