Ss 31: Research Applications

Research Applications

SS-31/elamipretide has been investigated across 10+ indication categories, with particular depth in cardiovascular, renal, ophthalmic, and aging research:

1. Barth Syndrome (Genetically-Confirmed Cardiolipin Deficiency) — TAFAZZIN gene mutations → cardiolipin deficiency → mitochondrial dysfunction. FDA Accelerated Approval (Sept 2025) for Forzinity™ based on TAZPOWER OLE data: +96.1 m 6MWT improvement (p=0.003) over 168 weeks; improved muscle strength and LV stroke volume.[3][9]
2. Primary Mitochondrial Myopathy (PMM) — MMPOWER Phase 1/2 (n=36): IV 0.25 mg/kg/h × 5 days → +64.5 m 6MWT vs +20.4 m placebo (p=0.053), significant dose-dependent benefit (p=0.014). MMPOWER-3 Phase 3 (n=218): failed primary endpoints (6MWT -3.2 m, p=0.69); post-hoc benefit in nDNA replisome mutation subgroup.[10]
3. Heart Failure — Sabbah et al. (2016): dogs with microembolization HF — 0.5 mg/kg SC × 3 months; LVEF improved 30% → 36% (p<0.05); NT-proBNP decreased 774 pg/mL (p<0.001); ATP/ADP ratio 1.16 vs 0.38 control. PROGRESS-HF Phase 2 (n=71): 4 or 40 mg SC × 28 days; no significant LVESV change. Phase 1 (n=36): IV 0.25 mg/kg/h × 4h → significant LV volume reductions.[6][5]
4. Ischemia-Reperfusion Injury — Cardiac, renal, and cerebral I/R: ATP recovery, tissue protection, mPTP prevention; demonstrated in multiple rodent/large animal models.[11]
5. Age-Related Macular Degeneration (Dry AMD) — ReCLAIM-2 Phase 2: 40 mg SC daily; failed primary endpoints (VA, GA area); slowed ellipsoid zone degradation. ReNEW Phase 3 (NCT06373731): n=360 target, 40 mg SC daily × 96 weeks; ongoing.[12]
6. Renal Disease — ARAS Phase 2a (n=14): IV during angioplasty → renal blood flow 262 vs 202 mL/min (p=0.04); improved GFR. Diabetic nephropathy: podocyte and brush border protection in rodent models.[13]
7. Aging and Sarcopenia — Campbell et al. (2019): 26-month female C57BL/6 mice — 3 mg/kg/day SC × 8 weeks; treadmill endurance nearly doubled (p<0.05); reversed ATPmax decline; no increase in mitochondrial content (bioenergetic quality improvement, not quantity).[4]
8. Cardiovascular / Atherosclerosis — Plaque reduction, CD36 downregulation; 55% inhibition of advanced plaque development in ApoE⁻/⁻ mice with chronic SS-31 treatment.[7]
9. Neurodegenerative Disorders — Alzheimer's disease: Zhao et al. (2019) LPS cognitive impairment mice — 5 mg/kg IP; escape latency reduced (p<0.01); hippocampal TNF-α/IL-6 reduced (p<0.05). Parkinson's disease, ALS — crosses BBB (small, water-soluble, cationic).[8]
10. Glaucoma / Diabetic Retinopathy — Retinal ganglion cell preservation; mitochondrial ROS reduction in retinal neurons; topical ophthalmic formulation studied in LHON trial.[12]