SS-31

elamipretide, Bendavia, MTP-131, Forzinity (US brand name)

Immune & bioregulators

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Elamipretide received FDA accelerated approval in 2025 for Barth syndrome, a rare genetic mitochondrial disorder †. For every other use it is an investigational or unapproved compound. This page explains the published science; grey-market "SS-31" is not the approved product.

Summary

Class: Synthetic tetrapeptide (D-Arg–dimethyl-Tyr–Lys–Phe-NH₂), one of the Szeto-Schiller series; cell-permeable and mitochondria-targeted
Mechanism: Binds cardiolipin in the inner mitochondrial membrane, stabilising cristae structure and the electron-transport chain so cells make more ATP and leak fewer free radicals
Routes studied: Subcutaneous daily injection (approved use and most trials); intravenous infusion (cardiac and kidney trials); topical eye drops (dry AMD)
Dose range reported: Barth syndrome label: 40 mg subcutaneous once daily (patients ≥30 kg) †. Trials in other conditions: 0.01–0.25 mg/kg/h IV infusions; 4–40 mg/day subcutaneous. Community: widely variable, often 5–20 mg/day subcutaneous — community-reported, and typically below trial doses
Half-life: Roughly 2–4 hours in plasma after subcutaneous dosing; tissue effects are thought to outlast plasma levels
Storage: Approved product: per label. Lyophilised research material: refrigerate, protect from light; reconstituted: refrigerate, use within ~4 weeks (community practice)
Regulatory status: Approved in the US for Barth syndrome (accelerated approval, 2025) †; investigational elsewhere and for all other indications

Doses are as reported in studies or by the community — never recommendations.

1What it is

SS-31 is a four-amino-acid synthetic peptide developed in the early 2000s by Hazel Szeto (Cornell) and Peter Schiller (Montreal), originally from work on opioid-like peptides. It turned out to concentrate about a thousand-fold inside mitochondria, where it sticks to cardiolipin, a fat molecule unique to the inner mitochondrial membrane that holds the energy-producing machinery in shape. Stealth BioTherapeutics has run the clinical programme under the name elamipretide, with trials in heart attack, heart failure, kidney disease, mitochondrial myopathy, Barth syndrome, dry age-related macular degeneration and Leber's hereditary optic neuropathy.

Most of those trials missed their primary endpoints. The exception that led to approval is Barth syndrome, an ultra-rare X-linked disorder in which cardiolipin itself is defective. It is one of the few compounds on this site with a real regulatory approval, and also one where the headline approval is far narrower than the online enthusiasm suggests.

2How it's thought to work

Cardiolipin binding. elamipretide binds cardiolipin and prevents cytochrome c from flipping into a peroxidase that destroys the membrane during stress (Birk 2013, J Am Soc Nephrol).

Cristae and supercomplexes. by stabilising membrane curvature it keeps respiratory-chain complexes assembled, improving electron flow and ATP output.

Less oxidative stress. fewer electrons leak to form superoxide, so downstream oxidative damage falls.

Not an antioxidant in the usual sense. it does not scavenge free radicals directly; it reduces their production at source.

Proposed: binds cardiolipin in the folded inner membrane of mitochondria, keeping the energy-producing complexes close together so fewer free radicals leak.Schematic — not to scale

The mechanism is unusually well characterised for a peptide, in cells, isolated mitochondria and animals (Szeto 2014, Br J Pharmacol). The clinical trials are where the story gets complicated.

3What the research shows

Graded A/B

Barth syndrome

TAZPOWER: a 12-patient randomised, double-blind, placebo-controlled crossover trial (12 weeks per arm, 40 mg/day) did not meet its primary endpoints of six-minute walk distance and fatigue. The open-label extension (up to 168 weeks) reported progressive improvements in walk distance, muscle strength and cardiac stroke volume compared with (Reid Thompson 2021, Genet Med; later extension reports). FDA granted accelerated approval in 2025 on the basis of muscle-strength data, with a confirmatory requirement †. Tiny numbers; uncontrolled long-term data. [3][9]

Graded A (negative)

Primary mitochondrial myopathy

MMPOWER-3 (n≈218, 40 mg/day for 24 weeks) did not improve six-minute walk distance or fatigue versus placebo (Karaa 2023, Neurology). Earlier Phase 1/2 studies had shown signals. [4]

Graded A (negative/neutral)

Heart failure

PROGRESS-HF (Phase 2, 4 or 40 mg/day for 28 days) showed no improvement in left-ventricular volumes or function versus placebo (Butler 2020, J Card Fail). A single-infusion study in HFrEF showed a short-lived reduction in LV volumes (Daubert 2017, Circ Heart Fail). [6][7]

Graded A (negative)

Acute myocardial infarction

EMBRACE STEMI: IV elamipretide during PCI did not reduce infarct size (Gibson 2016, Eur Heart J). [5]

Graded A (mixed)

Dry age-related macular degeneration

ReCLAIM-2 (Phase 2, daily ) missed its visual-function primary endpoint but reported slowed progression of ellipsoid-zone attenuation, an imaging marker of photoreceptor loss (Allingham 2022, Ophthalmol Sci). Phase 3 trials (ReNEW, ReGAIN) are ongoing †. [8]

Ageing, skeletal muscle and kidney in animals

Old mice given SS-31 showed rapid improvements in muscle mitochondrial function and exercise tolerance; rodent models of kidney ischaemia and diabetic kidney disease improved. The ageing claims that circulate online rest on this animal work, not on the human trials.

4Reported side effects and interactions

Literature-reported

the dominant adverse effect across trials is injection-site reaction — redness, itching, pain, swelling, bruising — in a majority of recipients, often leading to site rotation and occasionally discontinuation. Eosinophilia was reported in some long-term recipients †. Headache, nausea and dizziness at rates similar to placebo in most trials. No consistent signal of organ toxicity.

Community-reported

injection-site welts that can persist for days (very common), itching, fatigue, headache; some report a subjective increase in energy, others nothing.

Theoretical. improving mitochondrial function in all cells could in principle support tumour cells too; not observed in trials but not studied for this purpose. Pregnancy data absent.

Interactions. none identified in trials. The label for the approved product should be consulted.

Markers researchers commonly monitor

Marker	Why it's watched
Eosinophil count (on a CBC with differential)	eosinophilia has been reported with long-term use in trials †.
Creatine kinase and lactate	markers of muscle and mitochondrial stress used in the myopathy trials.
Six-minute walk distance and grip or knee-extensor strength	the functional endpoints used in Barth and myopathy trials.
Echocardiographic stroke volume and ejection fraction	cardiac endpoints in Barth and heart-failure trials.
Injection-site diary	the most common adverse effect; tracked systematically in trials.
General baseline: CBC, CMP, liver and kidney function

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

Research material typically comes in 10 mg or 50 mg vials because doses are in milligrams. with ; the peptide is fairly stable in solution. Because injection-site reactions are the main issue in trials, researchers often use larger dilution volumes and rotate sites.

Open in calculator, pre-loaded →

6Commonly studied alongside

MOTS-c and humanin (community "mitochondrial stack"; no combined study), NAD⁺ precursors, CoQ10 (as a comparator or background therapy in mitochondrial disease).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	FDA accelerated approval (2025) as Forzinity for Barth syndrome in patients weighing ≥30 kg; all other uses investigational or unapproved. Grey-market SS-31 is not the approved product †
European Union	Not authorised; orphan designation for Barth syndrome exists †
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
Sport	Previously S0 (non-approved); status after US approval should be checked against the current WADA list †

8Open questions

Why did a compound with such a clear mechanism fail most of its efficacy trials? Patient selection, dose and endpoint choice are all debated.
Does the Barth-syndrome benefit depend on the specific cardiolipin defect, so that it does not generalise to ordinary ageing?
Long-term safety beyond a few hundred patients.
Whether lower community doses have any pharmacological effect at all.

9References

1Szeto HH (2014). First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. PubMed · DOI
2Birk AV et al. (2013). The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. PubMed · DOI
3Reid Thompson W et al. (2021). A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome. Genet Med. PubMed
4Karaa A et al. (2023). Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial. Neurology. PubMed · DOI
5Gibson CM et al. (2016). EMBRACE STEMI study: a Phase 2a trial to evaluate the safety, tolerability, and efficacy of intravenous MTP-131 on reperfusion injury in patients undergoing primary percutaneous coronary intervention. Eur Heart J. PubMed · DOI
6Butler J et al. (2020). Effects of elamipretide on left ventricular function in patients with heart failure with reduced ejection fraction: the PROGRESS-HF phase 2 trial. J Card Fail. PubMed · DOI
7Daubert MA et al. (2017). Novel mitochondria-targeting peptide in heart failure treatment: a randomized, placebo-controlled trial of elamipretide. Circ Heart Fail. PubMed · DOI
8Allingham MJ et al. (2022). Elamipretide, a mitochondrial-targeted drug, for the treatment of subjects with dry AMD: the ReCLAIM-2 trial. Ophthalmol Sci. PubMed
9FDA (2025). Approval documents for elamipretide (Forzinity) in Barth syndrome [verify]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

25 Oct 2026Profile published — awaiting medical review

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