SS-31

SS-31 (Bendavia, Elamipretide) is a cell-permeable tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) designed to scavenge mitochondrial ROS, stabilize cardiolipin, and optimize electron transport chain (ETC) function. Developed by Stealth BioTherapeutics, it’s in Phase 3 trials for mitochondrial diseases, heart failure, and neurodegeneration—promising 20–50% mitochondrial efficiency gains in models.

Unique: Accumulates 1000x in mitochondria; protects without affecting cytosol.

How It Works

Cardiolipin Binding: Restores inner membrane structure (ETC complexes I/II).
ROS Neutralization: Prevents superoxide at Complex I/III.
ATP Production: ↑ΔΨm, oxygen consumption 30%.
Anti-Apoptosis: ↓Cytochrome c release, Bax inhibition.

Pharmacokinetics: IV/subQ; half-life 2–4h; mitochondria half-life days.

Research Evidence

Condition	Key Studies/Effects
Mitochondrial Myopathy	Barth syndrome: 6-min walk ↑60% (Phase 2, Neurology 2021).
Heart Failure	LVEF ↑8%, biomarkers ↓ (Phase 2, JACC 2020).
Kidney Disease	eGFR preservation (MMRCT-01 trial).
Neuro	Alzheimer’s models: Aβ ↓, cognition ↑ (animal).
Aging/Longevity	Muscle function ↑, ROS -40% (rodents).

Phase 3: RePOWER (Barth), MMPOWER-3 (primary mitochondrial myopathy).

Protocols (Research Contexts)

Goal	Dose (mg/day)	Route/Frequency	Cycle
Mito Health	0.25–1mg/kg	SubQ daily	12–24 weeks
Performance	5–10mg	Pre-WO + PM	8 weeks
Neuroprotection	10–20mg	Split BID	Ongoing
Anti-Aging	5mg	Nightly	Long-term

Stack: w/ MitoQ, PQQ, NAD+ boosters.
Vial: 10–50mg lyophilized; bac water recon.

Benefits Breakdown

Energy/Endurance: Fatigue resistance ↑.
Muscle Recovery: Oxidative damage ↓.
Cognitive: Brain mito protection.
Cardio/Renal: Organelle rescue.
Longevity: Sirtuin/AMPK synergy.

Side Effects & Safety

Common (Mild)	Trial-Reported	Notes
Injection site, headache	Transient HR ↑	Phase 2: 94% completion
Nausea	None serious	IV preferred clinically

Toxicity: Clean; no genotox.
Status: Orphan drug for mito diseases.

Comparisons

Peptide	Target	Delivery	Stage
SS-31	Mitochondria inner	Mito-specific	Phase 3
MOTS-c	Nuclear-mito	Exercise-like	Preclinical
Humanin	Cytoprotective	Broad	Research
SS-02	Cardiolipin alt	Similar	Early