MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
SS-31 Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
SS-31 (elamipretide, MTP-131) is a mitochondria-targeted aromatic-cationic tetrapeptide developed by Hazel Szeto and Peter Schiller at Weill Cornell that selectively binds cardiolipin on the inner mitochondrial membrane, stabilizing cristae architecture, preserving electron transport chain supercomplex assembly, and preventing peroxidation of cardiolipin by cytochrome c, which is the proximal trigger for intrinsic apoptosis. Unlike triphenylphosphonium-conjugated antioxidants, SS-31 accumulates independently of membrane potential, so it retains activity when delta-psi-m collapses during ischemia. Researchers study it for primary mitochondrial myopathy, Barth syndrome, heart failure with preserved ejection fraction, ischemia-reperfusion injury in heart and kidney, geographic atrophy in dry age-related macular degeneration, and sarcopenia in aging. On 19 September 2025 the FDA granted accelerated approval for elamipretide HCl (FORZINITY) as the first therapy for Barth syndrome in patients greater than or equal to 30 kg (PMID 33046859), built on Szeto's foundational cardiolipin-binding work (PMID 24117165).
Reconstitute: Add 1 mL bacteriostatic water → 10 mg/mL concentration.
Easy measuring: At 10 mg/mL, 1 unit = 0.01 mL = 0.1 mg (100 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen at −20 °C; reconstituted refrigerated at 2–8 °C; use within 4 weeks.
Plasma half-life: Approximately 2 hours after subcutaneous dosing, with Cmax at 1 to 2 hours. Tissue retention in heart, kidney, and muscle far exceeds plasma exposure due to high-affinity cardiolipin binding.
Onset of pharmacodynamic effects: Mitochondrial coupling improvements have been measured within days in preclinical models, while clinical endpoints such as knee extensor strength in TAZPOWER required 24 to 48 weeks of daily dosing.
Regulatory status: FDA accelerated approval September 2025 (FORZINITY) for Barth syndrome only. All other uses including mitochondrial myopathy, HFpEF, and AMD remain investigational with continued approval contingent on confirmatory benefit.
Mechanism distinction: Structural antioxidant that stabilizes cardiolipin rather than scavenging free radicals directly. Activity is preserved under collapsed membrane potential, distinguishing it from MitoQ or SkQ1.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid vigorous shaking to prevent foaming.
Gently swirl/roll until fully dissolved (clear solution).
Inject slowly over several seconds; wait briefly before withdrawing the needle to prevent leakage.
Administration: Do not aspirate for subcutaneous injections[11]; inject slowly and steadily over 3–5 seconds; wait 5–10 seconds before withdrawing the needle to minimize leakage.
Interactive SS-31 Syringe Calculator
Currently visualizing the 10 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 10mg dry powder in 1mL water yields 10.00 mg/mL. To evaluate a 250mcg dose, pull to 2.5 units (3 syringe ticks).
U-100 Syringe Representation
2.5 Units (3 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week | Daily Dose (mg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 5 mg (5000 mcg) | 50 units (0.50 mL) |
| Weeks 3–8 | 10 mg (10,000 mcg) | 100 units (1.0 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
| Week | Daily Dose (mg) | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 5 mg (5000 mcg) | 50 units (0.50 mL) |
| Weeks 3–4 | 10 mg (10,000 mcg) | 100 units (1.0 mL) |
| Weeks 5–8 | 15 mg (15,000 mcg) | Split: 2 × 75 units (0.75 mL each) |
| Optional Weeks 9–12 | 20 mg (20,000 mcg) | Split: 2 × 100 units (1.0 mL each) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 10 mg vial.
Peptide Vials (SS‑31, 10 mg each):
- check8 weeks (Standard: 5–10 mg/day) ≈ 50 vials
- check12 weeks (Standard maintenance at 10 mg/day) ≈ 77 vials
- check12 weeks (Advanced: escalating to 15 mg/day) ≈ 105 vials
Insulin Syringes (U‑100, 1 mL capacity):
- checkPer week (standard dosing): 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
- checkAdvanced protocols with split injections may require 2 syringes per day for higher doses
Bacteriostatic Water (30 mL bottles): Use 1.0 mL per vial for reconstitution.
- check8 weeks (50 vials): 50 mL → 2 × 30 mL bottles
- check12 weeks (77 vials): 77 mL → 3 × 30 mL bottles
- check12 weeks (105 vials, advanced): 105 mL → 4 × 30 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100‑count boxes
- check12 weeks: 168 swabs → recommend 2 × 100‑count boxes
Mechanism of Action (MOA)
SS-31 is one of the Szeto-Schiller (SS) peptides, a family of cell-permeable analogs that concentrate 1,000 to 5,000 fold within the inner mitochondrial membrane through electrostatic and hydrophobic interactions with cardiolipin, an anionic phospholipid almost exclusively located on the matrix-facing leaflet of the inner mitochondrial membrane [1][2]. Unlike triphenylphosphonium-conjugated antioxidants, SS-31 does not depend on membrane potential for accumulation, so it continues to localize to mitochondria even when delta-psi-m collapses during ischemia. Once bound to cardiolipin, the peptide reorganizes membrane electrostatics, stabilizes supercomplexes of respiratory chain complexes I/III/IV, and prevents peroxidation of cardiolipin by cytochrome c, which is the proximal trigger for cytochrome c release and intrinsic apoptosis [2][4]. The net effect is faster ATP recovery after ischemic insult, reduced mtROS generation, preserved cristae architecture on electron microscopy, and improved mitophagy of damaged organelles. Pharmacokinetic studies in healthy volunteers show that subcutaneous elamipretide reaches Cmax within 1 to 2 hours, with a plasma half-life of approximately 2 hours, but tissue retention in heart, kidney, and skeletal muscle far exceeds plasma exposure because of the high-affinity cardiolipin binding [7]. The standard research route is subcutaneous injection in the abdomen or thigh once daily; intravenous infusion has been used in ischemia-reperfusion trials (EMBRACE STEMI) but offered no advantage over subcutaneous dosing for chronic indications. In MMPOWER-3, 40 mg/day for 24 weeks was used in adults with primary mitochondrial myopathy [3]. In TAZPOWER (Barth syndrome), 40 mg/day was given long term with weight-adjusted titration in pediatric patients [6]. ReCLAIM-2 used 40 mg/day subcutaneously for 48 weeks in dry age-related macular degeneration with geographic atrophy [5]. Downstream effects documented across these programs include increased 6-minute walk distance, improved knee extensor strength, attenuated ellipsoid zone loss on OCT, and increased cardiac stroke volume on MRI. Common research uses include mitochondrial myopathy, heart failure with preserved ejection fraction, Barth syndrome, dry AMD, sarcopenia in aging, and neurodegenerative models in which mitochondrial dysfunction is a central pathology. SS-31 does not scavenge free radicals directly the way vitamin E does; its antioxidant effect is structural, derived from preserving the cardiolipin-cytochrome c interaction and preventing the futile electron leak that generates superoxide at complex I and III. The pharmacological distinction between SS-31 and mitochondria-targeted antioxidants such as mitoquinone (MitoQ) or SkQ1 is important: these molecules accumulate in mitochondria via lipophilic cations driven by membrane potential and then donate electrons to scavenge reactive species, whereas SS-31 binds cardiolipin and stabilizes the substrate of oxidative damage rather than reacting with ROS species directly. This mechanism explains why SS-31 retains activity in conditions where membrane potential is collapsed (ischemia, severe oxidative stress), and why it continues to protect mitochondrial structure under conditions where antioxidant cation-conjugated compounds lose accumulation. Long-term safety data across MMPOWER, TAZPOWER, ReCLAIM, EMBRACE STEMI, PROGRESS-HF, and TRIAGE-HF programs has accumulated to over 1,000 cumulative patient-years of exposure without identification of clinically meaningful off-target toxicities in liver, kidney, or hematologic parameters [7].
Clinical Trial Efficacy Highlights
- starMMPOWER-3 was a 24-week double-blind randomized placebo-controlled phase 3 trial of 218 adults with primary mitochondrial myopathy receiving 40 mg/day subcutaneous elamipretide; the trial did not meet its co-primary endpoints of 6-minute walk distance and Primary Mitochondrial Myopathy Symptom Assessment, although a long-term open-label extension showed maintenance of function over 48 weeks [3].
- starThe TAZPOWER trial in Barth syndrome (n=12) showed sustained improvement in knee extensor strength and the Barth Syndrome Symptom Assessment over 168 weeks of open-label 40 mg/day subcutaneous elamipretide, supporting the FDA accelerated approval of FORZINITY in September 2025 [6][8].
- starBirk and colleagues demonstrated in a rat model of renal ischemia-reperfusion that SS-31 administered before reperfusion accelerated ATP recovery, preserved cristae architecture on electron microscopy, and reduced acute kidney injury, mechanistically linked to high-affinity cardiolipin binding on the inner mitochondrial membrane [4].
- starThe phase 2 ReCLAIM-2 trial of 176 patients with dry age-related macular degeneration and geographic atrophy demonstrated that 40 mg/day subcutaneous elamipretide for 48 weeks slowed ellipsoid zone attenuation versus placebo, supporting a phase 3 program in AMD [5].
- starEMBRACE STEMI evaluated intravenous elamipretide given at first medical contact in patients undergoing primary PCI for anterior ST-elevation myocardial infarction; the trial did not meet its primary endpoint of infarct size reduction by cardiac MRI but established cardiovascular safety of acute IV dosing [9].
- starPreclinical work by Szeto and colleagues in aged mice showed that 8 weeks of SS-31 reversed age-related decline in muscle ATP production, restored mitochondrial coupling, and improved fatigue resistance, providing the rationale for ongoing sarcopenia trials [1][7].
- starIn an early-phase study in heart failure with preserved ejection fraction, a single 4-hour intravenous infusion of elamipretide produced a dose-dependent reduction in left ventricular end-diastolic volume and improved diastolic function on echocardiography, supporting development for HFpEF [10].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningInjection site reactions including erythema, pruritus, induration, and transient pain are the most common adverse events reported across MMPOWER, TAZPOWER, and ReCLAIM trials, occurring in roughly 40 to 80 percent of treated participants but rarely leading to discontinuation [3][6].
- warningHeadache and mild dizziness have been reported in 5 to 15 percent of subjects, generally within the first 2 hours after dosing and self-limited, possibly reflecting transient vasoactive effects of the peptide on endothelial mitochondria.
- warningGastrointestinal symptoms such as nausea and diarrhea were reported in subsets of MMPOWER participants but were not consistently different from placebo, suggesting they reflect underlying disease rather than drug effect.
- warningHypersensitivity reactions, including urticaria and angioedema, have been described uncommonly and are listed as warnings in the FORZINITY prescribing information; anaphylaxis has not been reported in published trials.
- warningBecause elamipretide is a synthetic cationic peptide, it can theoretically interact with anionic phospholipid surfaces beyond cardiolipin, but no clinically meaningful off-target toxicities in liver, kidney, or hematologic parameters have emerged across more than 1,000 cumulative patient-years of exposure.
- warningPharmacokinetic studies show no significant accumulation with daily dosing, and no QT prolongation was observed in dedicated thorough QT studies, supporting cardiovascular safety at therapeutic doses [7].
- warningBecause no human pregnancy data exist, FORZINITY labeling advises against use during pregnancy and lactation; animal reproductive studies have not demonstrated teratogenicity at supratherapeutic doses.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical SS-31 dosage?expand_more
Across MMPOWER-3, TAZPOWER, and ReCLAIM-2, the studied dose was 40 mg/day subcutaneous, with body-weight titration in pediatric Barth syndrome (greater than or equal to 30 kg). Research protocols commonly evaluate 30 to 80 mg/day SC for adults, given once daily in the abdomen or thigh.
How is SS-31 used in research protocols?expand_more
SS-31 is administered by daily subcutaneous injection, with treatment cycles spanning 4 to 48 weeks in published trials. Outcome measures focus on mitochondrial function (peak VO2, 6-minute walk, knee extensor strength), cardiac MRI parameters, and ellipsoid zone preservation on OCT in retinal studies.
Can SS-31 be combined with other peptides?expand_more
In research settings SS-31 is sometimes paired with mitochondrial cofactors (coenzyme Q10, nicotinamide riboside) and, in cardiomyopathy models, with standard heart failure therapy. Combinations with growth-promoting peptides have not been formally studied and would not share a mechanistic target.
What are the side effects of SS-31?expand_more
Most adverse events are local injection site reactions (erythema, induration, pruritus) that resolve within 24 to 48 hours. Headache, dizziness, and mild gastrointestinal symptoms occur in fewer than 15 percent of subjects. Serious hypersensitivity reactions are rare but listed in the FORZINITY label.
Is SS-31 FDA approved?expand_more
Yes. The FDA granted accelerated approval to elamipretide HCl (FORZINITY) on 19 September 2025 for Barth syndrome in adult and pediatric patients greater than or equal to 30 kg. Continued approval is contingent on confirmatory clinical benefit; SS-31 is otherwise unapproved for other indications.
Academic References & Study Citations
Szeto HH. First-in-class cardiolipin-protective compound as a therapeutic agent to restore mitochondrial bioenergetics. Br J Pharmacol. 2014;171(8):2029-2050. View Scientific Paper →
Mitchell W, Ng EA, Tamucci JD, et al. The mitochondria-targeted peptide SS-31 binds lipid bilayers and modulates surface electrostatics as a key component of its mechanism of action. J Biol Chem. 2020;295(21):7452-7469. View Scientific Paper →
Karaa A, Bertini E, Carelli V, et al. Efficacy and safety of elamipretide in adults with primary mitochondrial myopathy: randomized controlled MMPOWER-3 trial. Neurology. 2023;101(3):e238-e252. View Scientific Paper →
Birk AV, Liu S, Soong Y, et al. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. J Am Soc Nephrol. 2013;24(8):1250-1261. View Scientific Paper →
Mettu PS, Allingham MJ, Cousins SW. Phase 2 ReCLAIM-2 trial of elamipretide in geographic atrophy secondary to dry age-related macular degeneration. Ophthalmology Retina. 2024;8(7):683-693. View Scientific Paper →
Reid Thompson W, Hornby B, Manuel R, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome (TAZPOWER). Genet Med. 2021;23(3):471-478. View Scientific Paper →
Sabbah HN, Gupta RC, Singh-Gupta V, Zhang K, Lanfear DE. Abnormalities of mitochondrial dynamics in the failing heart: normalization following long-term therapy with elamipretide. Cardiovasc Drugs Ther. 2018;32(4):319-328. View Scientific Paper →
Stealth BioTherapeutics. FORZINITY (elamipretide) prescribing information; FDA accelerated approval announcement, September 2025. View Scientific Paper →
Gibson CM, Giugliano RP, Kloner RA, et al. EMBRACE STEMI study: a phase 2a trial of elamipretide in patients undergoing primary percutaneous coronary intervention for anterior ST-elevation myocardial infarction. Eur Heart J. 2016;37(16):1296-1303. View Scientific Paper →
Daubert MA, Yow E, Dunn G, et al. Novel mitochondria-targeting peptide in heart failure treatment: a randomized clinical trial of elamipretide. Circ Heart Fail. 2017;10(12):e004389. View Scientific Paper →