SS-31, also known as Elamipretide, is an investigational peptide. It is designed to specifically target and restore mitochondrial function, the cell’s energy centers. This peptide addresses various conditions associated with a decline in cellular energy production.
The Role of Mitochondria in Cellular Health
Mitochondria generate adenosine triphosphate (ATP), the cell’s main energy currency. ATP fuels nearly all cellular activities, from muscle contraction to nerve impulse transmission. This constant energy supply is fundamental for cell maintenance, growth, and repair.
When mitochondrial function declines, cells experience a significant reduction in available energy. This dysfunction also increases oxidative stress, damage caused by reactive oxygen species (ROS). Over time, this cellular energy deficit and oxidative damage can accelerate cellular aging and lead to cell death. Mitochondrial impairment is linked to age-related and chronic diseases.
SS-31’s Unique Mechanism of Action
SS-31 is a small mitochondrially-targeted tetrapeptide that distinguishes itself from general antioxidants due to its specific action. It penetrates cell membranes and accumulates within the inner mitochondrial membrane. There, SS-31 binds to cardiolipin, a phospholipid key to this membrane.
This binding stabilizes the inner mitochondrial membrane. By interacting with cardiolipin, SS-31 improves the electron transport chain’s efficiency, which generates ATP. This boosts ATP production and reduces harmful reactive oxygen species, lowering oxidative stress. The peptide’s ability to modulate the membrane’s electrostatic properties contributes to its protective effects on mitochondria.
Key Areas of Clinical Research
Elamipretide has been investigated in clinical trials for conditions where mitochondrial dysfunction plays a role. It has been studied for Barth syndrome, an ultra-rare genetic disease with severe muscle weakness, exercise intolerance, and cardiomyopathy, where a cardiolipin deficit is central.
The peptide is also undergoing late-stage clinical studies for ophthalmic diseases, such as dry Age-Related Macular Degeneration (AMD). Dry AMD involves progressive damage and death of retinal photoreceptors, leading to vision loss, a process where mitochondrial dysfunction is implicated. Phase 3 trials, ReNEW and ReGAIN, are evaluating Elamipretide’s ability to slow photoreceptor loss in dry AMD patients.
Elamipretide is also in a Phase 3 clinical trial for primary mitochondrial myopathy, a rare neuromuscular disorder impairing muscle function due to mitochondrial issues. Beyond these, research has explored its potential in cardiovascular conditions, showing promise in improving cardiac function by stabilizing mitochondrial activity. Furthermore, its protective effects on renal function have been investigated in conditions like diabetic neuropathy and chronic kidney disease.
Regulatory Status and Future Outlook
SS-31 (Elamipretide) remains an investigational drug, not yet approved by the U.S. Food and Drug Administration (FDA). Stealth BioTherapeutics, the developer, is pursuing its regulatory pathway. For Barth syndrome, Elamipretide has received several special regulatory designations from the FDA, including Orphan Drug, Fast Track, Priority Review, and Rare Pediatric designations.
Despite these designations and a positive advisory committee vote, the FDA recently issued a complete response letter for its application for Barth syndrome, citing the need for additional data and analyses, though it has proposed an accelerated approval pathway for a potential resubmission. This indicates the therapy’s potential for this ultra-rare condition, even as the regulatory journey continues. As research progresses, Elamipretide stands as a promising, first-in-class therapy addressing mitochondrial dysfunction across challenging conditions.