SS-31 (10 mg)

At a Glance

SS-31 (Elamipretide) is an aromatic-cationic tetrapeptide that binds cardiolipin on the inner mitochondrial membrane to stabilize electron transport chain supercomplexes, reduce ROS generation, and restore ATP production in ischemic or failing tissue.[1] It has completed randomized phase 2 trials in heart failure (IV route, REPAIR-SHF) and is under study in Barth syndrome (a mitochondrial cardiomyopathy) via SC administration.

• Reconstitute: Add 1.0 mL bacteriostatic water → 10 mg/mL concentration.
• Standard dose: 5–10 mg subcutaneous once daily (research context).
• Easy measuring: At 10 mg/mL on a U-100 syringe, 1 unit = 0.01 mL = 0.1 mg. A 5 mg dose = 50 units / 0.5 mL.
• Storage: Lyophilised: freeze at −20 °C; reconstituted: refrigerate at 2–8 °C; use within 4 weeks.

Overview

• Goal: Restore mitochondrial bioenergetics by stabilizing cardiolipin-dependent ETC supercomplexes and reducing mitochondrial ROS.[1]
• Schedule: Once-daily subcutaneous injection.
• Dose range: 2.5–10 mg SC once daily; clinical trials used 40 mg/day SC in Barth syndrome and 0.05–0.25 mg/kg IV in REPAIR-SHF.
• Reconstitution: 1.0 mL BAC water per 10 mg vial → 10 mg/mL.
• Injection site: Abdomen, thigh, or upper arm; rotate daily.

What You'll Need

Plan based on a 4-week cycle at 5 mg once daily (28 injections, 140 mg total).

• SS-31 Vials (10 mg each): 140 mg needed ÷ 10 mg per vial → 14 vials.
• Insulin Syringes (U-100, 0.5 mL / 50-unit or 1 mL / 100-unit): 28 injections → 28 syringes.
• Bacteriostatic Water (10 mL bottles): 1.0 mL per vial → 2 × 10 mL bottles (covers 14 vials).
• Alcohol Swabs: 2 per injection → 56 swabs per 4-week cycle.

How to Reconstitute

1. Allow frozen lyophilised vial to reach room temperature (10–15 minutes).
2. Draw 1.0 mL bacteriostatic water with a sterile syringe.
3. Inject slowly down the inner vial wall.
4. Gently swirl until fully dissolved — do not shake. Solution should be clear and colourless.
5. Label with reconstitution date; refrigerate at 2–8 °C, protected from light. Use within 4 weeks.

Dosing Schedule

Start at 2.5 mg once daily for 3–5 days to assess for injection-site reactions, then escalate to 5–10 mg as tolerated. Injection-site reactions (redness, induration) are the most commonly reported adverse effect across elamipretide SC dosing in published clinical programs.

Protocol Details

• Starting dose: 2.5 mg (25 units / 0.25 mL) once daily SC for Days 1–5.
• Standard dose: 5 mg (50 units / 0.5 mL) once daily from Day 6+.
• Higher dose: 10 mg (100 units / 1.0 mL) once daily for advanced protocols.
• Cycle: 4–12 weeks; published Barth syndrome clinical programs have run up to 36 weeks.
• Injection site: Rotate systematically; avoid areas with existing induration or erythema.

Storage

• Lyophilised: Store at −20 °C (−4 °F); protect from moisture and light.
• Reconstituted: Refrigerate at 2–8 °C. Do not freeze. Use within 4 weeks.
• Appearance: Clear, colourless solution. Discard if cloudy, discoloured, or particulate.

How SS-31 Works

SS-31 (D-Arg-2′,6′-Dmt-Lys-Phe-NH₂) is a 4-amino acid aromatic-cationic peptide designed to penetrate both mitochondrial membranes without relying on membrane potential (ΔΨm). Its alternating cationic (D-Arg, Lys) and aromatic (Dmt, Phe) residues enable spontaneous inner-membrane uptake, making it effective in severely depolarized mitochondria where potential-driven compounds lose targeting ability.[1]

At the inner membrane, SS-31 binds selectively to cardiolipin — the phospholipid that scaffolds the respiratory supercomplexes (Complexes I, III, and IV). Cardiolipin integrity is required for optimal electron channeling through these supercomplexes. Under ischemia, oxidative stress, or aging, cardiolipin peroxidation destabilizes supercomplex architecture, impairs electron transfer, and increases ROS generation at Complexes I and III. By stabilizing cardiolipin, SS-31 preserves supercomplex integrity, restores efficient ATP synthesis, and reduces electron leak to superoxide.[1]

Additionally, cardiolipin anchors cytochrome c to the inner membrane for electron shuttling between Complexes III and IV. Cardiolipin loss releases cytochrome c into the cytosol, triggering apoptosis. SS-31's cardiolipin binding maintains this interaction.[1]

For mechanism, evidence, and trial data, see What Is SS-31 (Elamipretide)?

Good to Know

• Injection-site reactions are expected: Redness, pain, and induration at the SC injection site are expected with elamipretide SC dosing, consistent with published clinical programs; reactions have not required treatment discontinuation.
• Not FDA-approved: SS-31 is investigational; it has FDA Fast Track designation for Barth syndrome but remains in clinical development.
• Membrane potential-independent uptake distinguishes SS-31 from older mitochondria-targeted cationic compounds such as MitoQ, which require intact ΔΨm.[1]
• WADA status: Not individually named on the WADA Prohibited List; athletes should seek written confirmation from their Anti-Doping Organization.
• One vial per injection at 10 mg: The 10 mg vial reconstituted with 1.0 mL yields a single full-dose injection at the 10 mg level; partially used vials should be stored refrigerated and used within the stability window.

Tips for Best Results

• Administer at a consistent time each day to maintain steady exposure.
• Rotate injection sites systematically (e.g., left abdomen → right abdomen → left thigh → right thigh) and document each site to track induration patterns.
• If injection-site reactions are persistent at one site, extend rest periods before reusing that location.
• Apply a cold pack briefly to the injection site before and after injection to reduce local discomfort and blunt the inflammatory response.

Injection Tips

• Clean the vial stopper and injection site with separate alcohol swabs; allow both to air-dry fully before proceeding.[4]
• Use a 29–31 gauge insulin syringe (5/16″ to 1/2″ needle); draw the calculated dose precisely.
• Pinch a fold of skin and insert the needle at 45° into subcutaneous fat (90° is acceptable with a short needle into a well-pinched fold).
• Inject slowly over 2–3 seconds. Do not aspirate. Withdraw the needle, apply gentle pressure, and do not rub.
• Dispose of each syringe in a sharps container immediately after use.