What is SS-31 Peptide?
SS-31, also known by its generic name elamipretide and brand name Forzinity, is a synthetic tetrapeptide specifically designed to penetrate and accumulate within the mitochondria of cells. Discovered by researchers at Weill Cornell Medical College, this small, cell-permeable molecule was developed to address diseases rooted in mitochondrial dysfunction. Unlike traditional antioxidants that indiscriminately scavenge free radicals, SS-31 is uniquely targeted to the inner mitochondrial membrane, allowing it to act precisely where the majority of cellular energy is produced and where oxidative damage is most prevalent.
Mechanism of Action: How SS-31 Protects Mitochondria
SS-31's therapeutic effects stem from its ability to interact directly with cardiolipin, a unique phospholipid found almost exclusively in the inner mitochondrial membrane. By binding to cardiolipin via electrostatic and hydrophobic interactions, SS-31 stabilizes the membrane, which is critical for maintaining mitochondrial structure and function.
Its key mechanisms include:
- Stabilizing Cardiolipin: The peptide prevents the peroxidation of cardiolipin, which can disrupt mitochondrial integrity and lead to energy failure.
- Enhancing ATP Production: By optimizing the interactions within the electron transport chain, SS-31 improves the efficiency of adenosine triphosphate (ATP) synthesis, providing more energy for the cell.
- Reducing Oxidative Stress: SS-31 scavenges mitochondrial reactive oxygen species (ROS) at their source, reducing the damage they can inflict on DNA, proteins, and lipids.
- Inhibiting Apoptosis: By protecting mitochondrial integrity and preventing the release of pro-apoptotic factors, SS-31 helps prevent premature cell death.
Approved and Investigational Uses of SS-31
While research has explored many potential applications, SS-31 has a specific FDA-approved indication and several other areas under investigation.
FDA-Approved Use: Barth Syndrome
As of September 2025, elamipretide (Forzinity) received accelerated FDA approval for the treatment of Barth syndrome (BTHS). BTHS is a rare, life-threatening genetic disorder caused by a mutation in the TAFAZZIN gene, which leads to a deficiency in cardiolipin remodeling and subsequent mitochondrial dysfunction. SS-31 helps improve muscle strength in affected individuals, addressing a key symptom of the disease, by stabilizing the mitochondrial inner membrane and improving bioenergetics.
Other Investigational and Preclinical Applications
Beyond its approved use, SS-31 has been investigated in numerous studies for other conditions linked to mitochondrial decline.
- Cardiovascular Health: Studies in animal models of heart failure and post-myocardial infarction have shown SS-31's ability to improve cardiac function, reduce oxidative stress, and prevent adverse remodeling. However, some clinical trials for heart failure have yielded mixed or inconclusive results.
- Neurodegenerative Diseases: SS-31 has shown promise in preclinical studies for protecting neurons in conditions like Alzheimer's disease, traumatic brain injury (TBI), and cerebral ischemia. Its ability to cross the blood-brain barrier and target mitochondria makes it a candidate for treating neuroinflammatory and cognitive deficits associated with aging.
- Kidney Disease: In animal models, SS-31 has been shown to protect kidney cells from various forms of injury, including ischemia-reperfusion injury, diabetic nephropathy, and obstruction. It works by reducing oxidative stress, protecting mitochondrial structure, and restoring ATP supply in renal tissue.
- Eye Conditions: Given that oxidative stress and mitochondrial dysfunction contribute to retinal damage, SS-31 has been studied for its potential in age-related macular degeneration (AMD) and glaucoma. Preclinical and early-stage clinical trials have shown a protective effect on retinal ganglion cells.
- Age-Related Muscle Decline: Research in aged mice demonstrated that SS-31 can reverse age-related declines in mitochondrial function, leading to improved muscle endurance and fatigue resistance.
Comparing SS-31 to Other Therapeutic Peptides
SS-31 stands out due to its specific action on cardiolipin and mitochondrial bioenergetics. Here is a comparison with other peptides also being researched for performance and longevity:
| Feature | SS-31 (Elamipretide) | MOTS-c | BPC-157 |
|---|---|---|---|
| Primary Target | Cardiolipin in inner mitochondrial membrane | AMPK activation | Angiogenesis, tissue repair |
| Core Mechanism | Stabilizes inner membrane, enhances ATP production, reduces oxidative stress | Improves glucose/fatty acid utilization, increases metabolic efficiency | Promotes blood flow, anti-inflammatory healing, tissue regeneration |
| Main Outcomes | Improved cellular energy, reduced oxidative damage, better endurance | Enhanced metabolic efficiency, exercise performance, weight management | Faster recovery from injury, tendon/gut repair |
| Typical Use Case | Mitochondrial dysfunction, age-related decline, Barth syndrome | Metabolic health, endurance training, body composition | Musculoskeletal injuries, gut repair, post-operative recovery |
Safety Profile and Clinical Trial Landscape
SS-31 is generally considered safe and well-tolerated, with most adverse effects being mild and related to the injection site. Clinical studies have shown no significant systemic adverse events in trials for various conditions. However, as with any investigational drug, some caution is advised:
- Side Effects: The most common side effects reported include injection site reactions, headache, dizziness, and mild gastrointestinal distress.
- Contraindications: Due to limited data, SS-31 is not recommended for pregnant or breastfeeding women. There are also theoretical risks regarding its effects on cell function for individuals with a history of cancer, so it should be avoided in this population.
- Clinical Trial Outcomes: It's important to note that while preclinical studies show broad promise, clinical trial results have been mixed. For instance, trials for primary mitochondrial myopathy and heart failure have failed to meet primary endpoints in some cases. This highlights the need for careful interpretation of results and the importance of continued research.
Conclusion
The SS-31 peptide represents a significant advancement in targeted mitochondrial therapy. Its FDA approval for Barth syndrome validates its potential to treat specific mitochondrial diseases by stabilizing cardiolipin and restoring cellular bioenergetics. Beyond this, a wide range of preclinical and clinical research suggests potential benefits for common age-related conditions like heart disease, neurodegeneration, and chronic kidney disease. While more research is needed to solidify its role in many of these areas, its unique mechanism of action makes it a promising candidate for addressing the underlying cause of many pathologies rooted in mitochondrial dysfunction. For more detailed clinical trial information, researchers and healthcare professionals can consult resources such as ClinicalTrials.gov.
