SS-31 Doses Used in Published Studies: What Researchers Reported

People searching for an "SS-31 dosage chart" are usually looking for a single number. The published literature does not contain one. SS-31 — the research designation for the mitochondria-targeted tetrapeptide also known as elamipretide — has been studied in cultured cells, in isolated mitochondria, in several rodent injury and ageing models, and in a human clinical programme that culminated in a first regulatory approval, and each of those settings used its own administration route, schedule and duration chosen to fit that experiment. This page summarises what researchers reported in each context, and explains why an experimental condition is not a recommendation.

This page is for educational purposes only and is not medical advice; consult a licensed physician about any medical question, medication or symptom. Nothing below is a protocol, and no part of it describes what any individual should do.

What the compound is, in the words of the literature

SS-31 is a short, positively charged peptide that accumulates in mitochondria and associates with the inner mitochondrial membrane. A proteomics study mapped its mitochondrial protein interaction landscape and reported that it engaged multiple inner-membrane proteins rather than a single receptor (PMID 32554501). A later genome-wide CRISPR screen identified phospholipid scramblase 3 as a biological target of the mitoprotective drug SS-31 (PMID 38530359). Narrative reviews have summarised this mechanistic work alongside the clinical programme and described the compound's structure, proposed mode of action and therapeutic potential as still-developing areas (PMID 39940712, PMID 40294492).

That mechanistic detail matters for the dosing question: because the peptide acts by partitioning into a membrane compartment, the concentration that reaches that compartment depends on delivery route, formulation and tissue perfusion — which is exactly why numbers do not carry across from a dish to an animal to a person.

Human clinical and regulatory context

The most consequential human data point is regulatory rather than experimental. A 2026 approval report in Drugs described elamipretide's first approval, a subcutaneously administered product developed for Barth syndrome and given on a once-daily basis in that indication (PMID 41335372). The exact strength, weight threshold and administration details belong to the approved prescribing information and to the clinician prescribing it; the approval summary is the primary source for readers who want the specifics as regulators accepted them (PMID 41335372).

The path to that approval has been reviewed in the cardiology literature. One review described the rationale for targeting mitochondrial dysfunction with elamipretide across heart failure and mitochondrial disease programmes (PMID 35037146), and a companion review framed the Barth syndrome cardiomyopathy work as a gradual rebuilding of a failed power grid, emphasising that changes in cardiac measures emerged over extended treatment rather than immediately (PMID 34623544). Both reviews are the appropriate place to read how researchers structured escalating and long-duration exposure in humans, because trial regimens differed by indication, by route (intravenous infusion in some early cardiovascular studies, subcutaneous injection in later programmes) and by whether the endpoint was acute physiology or months-long functional change (PMID 35037146, PMID 40294492).

Animal studies: species, route and duration as reported

Preclinical papers are where most of the searched-for "mg/kg" figures actually live — and they are species- and model-specific.

Neuroinflammation model in mice

A 2019 study in Journal of Neuroinflammation administered elamipretide (SS-31) systemically to mice challenged with lipopolysaccharide and reported improvement in mitochondrial dysfunction and in synaptic and memory impairment relative to untreated LPS-exposed animals (PMID 31747905). The study used injected administration over a short course timed around the inflammatory challenge; the milligram-per-kilogram figure and the number of dosing days are stated in the paper's methods, and they were selected to match a laboratory-induced insult in a small rodent (PMID 31747905).

Aged mouse hearts

A 2020 paper in Aging Cell compared SS-31 and nicotinamide mononucleotide as two paths to improve metabolism and function in aged hearts, administering the peptide daily to old mice over a multi-week course and reporting improvements in cardiac metabolic and functional measures (PMID 32779818). Notably, the researchers reported that the two interventions produced overlapping but non-identical effects, which is a reminder that the reported outcome was tied to the specific schedule and duration tested rather than to the molecule alone (PMID 32779818).

Traumatic spinal cord injury

A 2023 study reported that elamipretide alleviated pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilisation, with the peptide given systemically after the injury was produced (PMID 36609266). In models like this, timing relative to injury is as much a variable as amount, and the study's dosing window was built around the acute injury cascade (PMID 36609266).

Post-cardiac-arrest brain injury

A 2026 Neurotherapeutics study reported that SS-31 improved post-cardiac-arrest brain injury by inhibiting microglial ferroptosis and polarisation in an animal resuscitation model, again with administration beginning after the ischaemic event (PMID 41136322). The relevant exposure in that study was short and event-anchored, not chronic (PMID 41136322).

Cell and in vitro work: concentrations, not doses

In cultured systems there is no "dose" at all — there is a concentration in the medium. A 2025 study described an engineered construct, SS-31@Fer-1, applied to cardiomyocytes undergoing hypoxia/reoxygenation, and reported that the mitochondrially targeted formulation alleviated ferroptosis in those cells (PMID 39848110). Because the peptide there served as a targeting carrier combined with a second agent, the exposure in that study cannot be compared with free peptide given to an animal (PMID 39848110). The interaction-mapping and CRISPR-screen studies likewise worked in cells and isolated mitochondria, where the reported conditions describe an assay, not an organism (PMID 32554501, PMID 38530359).

How the study settings compare

This table describes published experimental conditions. It is not a set of suggested amounts, and no row should be read as applying to a person outside the setting described in the cited paper.

Why study doses do not become recommendations

1. Species scaling is not arithmetic. A milligram-per-kilogram amount that produced a measurable effect in mice reflects rodent metabolism, body surface area and clearance. The reviews of elamipretide's development describe human regimens arrived at through dedicated clinical study rather than by converting animal figures (PMID 35037146, PMID 41335372).
2. Route changes exposure. Intravenous infusion, subcutaneous injection and in-medium application are not interchangeable, and reviews of the mechanism note that mitochondrial accumulation depends on delivery and tissue context (PMID 40294492).
3. Formulation changes everything. The SS-31@Fer-1 construct was a carrier system, not free peptide, and its reported effect on ferroptosis cannot be attributed to an equivalent amount of unformulated peptide (PMID 39848110).
4. The model defines the endpoint. Studies in acute injury reported outcomes measured hours to days after an insult (PMID 36609266, PMID 41136322), whereas human cardiomyopathy work was described in terms of change accruing over months (PMID 34623544). Those are different questions with different exposure requirements.
5. Indication-specific approval is narrow. The first approval covered a defined rare-disease population under medical supervision (PMID 41335372); it did not establish dosing for ageing, athletic or general wellness contexts, and no cited paper addressed those uses.

Research-grade peptide material sold for laboratory work is generally labelled research use only and is not a medicine; the approved elamipretide product is a regulated prescription medicine described in the approval literature (PMID 41335372). Those two categories differ in identity testing, sterility, labelling and oversight.

Tolerability and Adverse Events: What Studies Report

The approval report for elamipretide described a subcutaneously injected product, and injection-site reactions have been the tolerability issue most consistently discussed in the subcutaneous programme as summarised in that report and in the mechanistic and clinical reviews (PMID 41335372, PMID 39940712). Reviews of the development programme also noted that not every trial met its primary endpoint, which is part of the safety-and-efficacy picture regulators weighed (PMID 35037146, PMID 34623544). None of the animal studies cited here were designed as human safety studies, and the researchers did not present them as such (PMID 31747905, PMID 32779818).

What remains unresolved

• Whether mechanistic targets identified in cells — including phospholipid scramblase 3 — explain the clinical findings remains an open research question (PMID 38530359, PMID 32554501).
• How long-duration exposure behaves outside the approved rare-disease setting has not been established in the cited literature (PMID 41335372, PMID 40294492).
• Whether rodent ageing findings translate to humans was not tested in the cited ageing study, which used mice (PMID 32779818).

For readers who want exact figures, the correct route is the primary papers themselves: each methods section states the concentration or milligram-per-kilogram amount, the route and the duration that the researchers actually used, together with the species and model those numbers belong to. Reading them in context is the difference between understanding an experiment and misreading it as instruction.

References

• Elamipretide: First Approval (Drugs, 2026)
• Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice (Journal of Neuroinflammation, 2019)
• Elamipretide: A Review of Its Structure, Mechanism of Action, and Therapeutic Potential (International Journal of Molecular Sciences, 2025)
• SS-31@Fer-1 Alleviates ferroptosis in hypoxia/reoxygenation cardiomyocytes via mitochondrial targeting (Biomedicine & Pharmacotherapy, 2025)
• Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects (Biomedicine & Pharmacotherapy, 2025)
• Targeting mitochondrial dysfunction with elamipretide (Heart Failure Reviews, 2022)
• Mitochondrial protein interaction landscape of SS-31 (PNAS, 2020)
• Genome-Wide CRISPR Screen Identifies Phospholipid Scramblase 3 as the Biological Target of Mitoprotective Drug SS-31 (JASN, 2024)
• Elamipretide alleviates pyroptosis in traumatically injured spinal cord by inhibiting cPLA2-induced lysosomal membrane permeabilization (Journal of Neuroinflammation, 2023)
• SS-31 and NMN: Two paths to improve metabolism and function in aged hearts (Aging Cell, 2020)
• SS-31 improves post-cardiac arrest brain injury by inhibiting microglial ferroptosis and polarization (Neurotherapeutics, 2026)
• Elamipretide for Barth syndrome cardiomyopathy: gradual rebuilding of a failed power grid (Heart Failure Reviews, 2022)