SS-31 — Peptide Protocol Wiki reference
patient_educationexpert_opinion · status: needs_provider_reviewDetails
Summary (generated — provider review required)
SS-31 (Elamipretide): Mitochondrial Peptide Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides? Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About SS-31 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides SS-31 Mitochondrial & Cellular Energy Anti-Aging & Longevity Vascular & Cardiovascular approved SS-31 Also known as: Elamipretide, Bendavia, MTP-131 Compare with 1 peptide Research compiled by Peptide Protocol Wiki 📅 Updated January 29, 2026 Citations Verified TL;DR SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane by binding to cardiolipin. It stabilizes electron transport chain supercomplexes and is in Phase 3 clinical trials for Barth syndrome, with additional investigation in heart failure and age-related mitochondrial dysfunction.
The original source document remains the source of truth. Generated summaries are not authoritative.
Linked assets (13) · phenotypes (1)
evidence_reference, safety_reference, dosing_reference, contraindication_reference, mechanism, monitoring_reference
Phenotypes: mitochondrial_dysfunction
Findings (71) · awaiting review (38)
outcome · pending
unction into measurable clinical outcomes in acute settings.
safety · pending
The long-term safety profile of chronic SS-31 administration is still being characterized.
dosing · pending
Covers neurotrophic mechanisms, approvals in 40+ countries, dosing, and safety data.
outcome · pending
Primary CK-MB endpoint not met Trends toward reduced infarct size on cardiac MRI
outcome · pending
Restore access No thanks, continue reading Related Reading Peptide MOTS-c mitochondrial-derived metabolic peptide Peptide Cerebrolysin neuroprotective peptide mixture Article Mitochondrial Peptides: The Next Frontier in Longevity How SS-31 works at the cellular level Overview of SS-31 benefits and applications Scientific Details Molecular Formula C32H49N9O5 Molecular Weight 639.8 Da CAS Number 736992-21-5 Sequence D-Arg-Dmt-Lys-Phe-NH2 What is SS-31?
safety · pending
SS-31 (Elamipretide): Mitochondrial Peptide Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?
dosing · pending
Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About SS-31 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides SS-31 Mitochondrial & Cellular Energy Anti-Aging & Longevity Vascular & Cardiovascular approved SS-31 Also known as: Elamipretide, Bendavia, MTP-131 Compare with 1 peptide Research compiled by Peptide Protocol Wiki 📅 Updated January 29, 2026 Citations Verified TL;DR SS-31 (Elamipretide) is a mitochondria-targeted tetrapeptide that selectively concentrates in the inner mitochondrial membrane by binding to cardiolipin.
outcome · pending
Electron Transport Chain Optimization # Through its stabilization of cardiolipin, SS-31 has been demonstrated to improve the efficiency of mitochondrial oxidative phosphorylation.
safety · pending
Browse all mitochondrial peptides → Table of Contents 📌 TL;DR • Selectively targets inner mitochondrial membrane • Phase 3 trials for Barth syndrome (TAZPOWER) • Stabilizes cardiolipin and electron transport chain • Investigated for heart failure and age-related decline Community-Reported Side Effects Anecdotal ?
dosing · pending
📋 Protocol Quick-Reference Mitochondrial protection and bioenergetic restoration (investigational, approved for Barth syndrome) 💉 Dosing Amount 40 mg subcutaneous daily (Phase 3 dose); or 5-10 mg daily (research community range) Frequency Once daily Duration 4-12 weeks (clinical trials); some research protocols use 4 weeks on, 2 weeks off 💊 Administration Route SC Schedule Once daily Timing Consistent time each day; no specific meal timing required ✓ Rotate injection sites 📅 Cycle Duration 4-12 weeks (clinical trials); some research protocols use 4 weeks on, 2 weeks off Rest Period 2 weeks off between cycles Repeatable Single cycle Preparation & Storage ✓ Ready-to-use — no reconstitution required Storage: Clinical trial supplies were stored under refrigerated conditions (2-8 degrees Celsius).
contraindication · pending
relevant for myopathy indications) BNP or NT-proBNP (if cardiac indication) When: Baseline Why: Baseline cardiac function marker 💡 Key Considerations → Contraindication: Investigational drug; no established contraindications outside clinical trial protocols; injection site reactions are common Subscribe to unlock this content Get weekly peptide research summaries, new study alerts, and protocol updates — free.
regulatory · pending
It has received Orphan Drug Designation and Fast Track Designation from the FDA for the treatment of Barth syndrome, a rare X-linked genetic disorder characterized by cardiomyopathy, skeletal myopathy, and neutropenia caused by mutations in the tafazzin gene that lead to defective cardiolipin remodeling.
mechanism · pending
Mechanism of Action # Szeto-Schiller Peptide Design # The SS peptide family was designed based on a structural motif that enables both cell penetration and mitochondrial targeting without requiring the mitochondrial membrane potential that is necessary for other mitochondria-targeted compounds such as triphenylphosphonium (TPP) conjugates.
mechanism · pending
Cardiolipin also plays a role in mitochondrial dynamics, cristae formation, and the regulation of apoptosis through its interaction with cytochrome c.
outcome · pending
By preserving cardiolipin integrity, SS-31 maintains the structural organization of ETC complexes and supercomplexes, thereby optimizing electron transfer efficiency and reducing electron leak that would otherwise generate additional ROS.
outcome · pending
This creates a virtuous cycle where reduced ROS production further protects cardiolipin from oxidative damage.
outcome · pending
Primary endpoint of CK-MB AUC reduction was not met, but cardiac MRI showed trends toward reduced infarct size.
outcome · pending
By restoring supercomplex formation, SS-31 reduces the generation of ROS at Complexes I and III, improves the coupling of electron transport to ATP synthesis, and increases the maximum capacity for oxidative phosphorylation.
outcome · pending
This improvement in mitochondrial bioenergetics is considered the primary mechanism underlying the therapeutic benefits observed in preclinical and clinical studies, rather than direct antioxidant scavenging activity that was originally hypothesized for the SS peptide series.
mechanism · pending
The peroxidase activity of the cytochrome c-cardiolipin complex is responsible for cardiolipin oxidation during mitochondrial stress, which in turn triggers the release of cytochrome c from the IMM and the initiation of the intrinsic apoptosis pathway.
outcome · pending
By inhibiting this peroxidase activity, SS-31 may provide cytoprotection against apoptotic cell death in addition to its bioenergetic benefits.
dosing · pending
The trial (Thompson WR et al., 2021) 1 enrolled 12 patients with genetically confirmed Barth syndrome and evaluated subcutaneous elamipretide (40 mg/day) in two 12-week treatment periods separated by a washout period.
outcome · pending
l demonstrated trends toward improvement in 6MWT distance and reported statistically significant improvements in the five-times sit-to-stand test, the primary 6MWT endpoint did not reach conventional statistical significance, attributed to the very small sample size inherent to ultra-rare disease trials 1 .
regulatory · pending
Stealth BioTherapeutics submitted a New Drug Application (NDA) to the FDA based on data from the TAZPOWER trial and open-label extension studies, but the FDA issued a Complete Response Letter requesting additional data.
monitoring · pending
Subsequent analyses and longer-term follow-up from open-label extension studies have provided additional evidence of clinical benefit, and the development program has continued under Larimar Therapeutics.
dosing · pending
The trial evaluated intravenous elamipretide administered as a single dose (0.25 mg/kg) at the time of reperfusion.
outcome · pending
While the primary endpoint of reduction in creatine kinase-MB (CK-MB) release was not met, the trial demonstrated trends toward reduced infarct size as measured by cardiac MRI 2 .
outcome · pending
The Phase 2 trial in heart failure with reduced ejection fraction (Daubert MA et a
dosing · pending
l., 2017) 3 evaluated 4 weeks of subcutaneous elamipretide (40 mg) and demonstrated improvements in left ventricular end-systolic volume and trends toward improved cardiac output 3 .
outcome · pending
These findings supported the concept that mitochondrial dysfunction contributes to heart failure pathophysiology and that targeting cardiolipin can improve cardiac function.
dosing · pending
Primary Mitochondrial Myopathy # A Phase 2 trial (Karaa A et al., 2018) 4 evaluated elamipretide (0.25 mg/kg daily IV) in patients with primary mitochondrial myopathy due to nuclear or mitochondrial DNA mutations.
outcome · pending
Numerical improvements in walking distance were observed but were not conclusive due to short treatment duration and small sample size 4 .
dosing · pending
Subcutaneous injection is the primary route of administration for chronic treatment, with intravenous administration used in acute care settings such as myocardial infarction.
outcome · pending
The pivotal TAZPOWER trial in Barth syndrome, while demonstrating trends toward benefit and significant improvements on some endpoints, did not meet its primary endpoint with conventional statistical significance, in part due to the very small sample size imposed by the rarity of the disease.
regulatory · pending
The FDA's Complete Response Letter underscored the regulatory challenges of demonstrating efficacy in ultra-rare diseases.
outcome · pending
In heart failure, while early-phase trials have shown promising signals, no Phase 3 trial has yet demonstrated a definitive clinical benefit.
outcome · pending
The EMBRACE STEMI trial's failure to meet its primary CK-MB endpoint, despite trends on imaging endpoints, illustrates the challenge of translating mechanistic improvements in mitochondrial f
safety · pending
While the open-label extension studies in Barth syndrome have provided encouraging safety data over months to years of treatment, the consequences of sustained cardiolipin stabilization and modified cytochrome c function over decades of use are unknown.
outcome · pending
Whether the benefits of SS-31 are sustained with long-term use or whether compensatory mechanisms could attenuate its effects over time is an open question.
regulatory · pending
The regulatory path forward for the Barth syndrome indication, following the FDA's Complete Response Letter, will likely require additional clinical data or analyses, potentially delaying patient access.
Processing
Processed into 20 searchable sections.