SS-31, also known as Elamipretide, is a synthetic, mitochondrial-targeting peptide designed to address cellular energy deficits and oxidative stress. This compound is a small tetrapeptide that selectively accumulates within the mitochondria, the cell’s powerhouses, where it works to improve their function. The primary goal of SS-31 is to stabilize and restore the integrity of the inner mitochondrial membrane, thereby enhancing the cell’s ability to produce energy. This approach positions the peptide as a promising investigational agent for a variety of conditions linked to mitochondrial dysfunction.
How SS-31 Works at the Cellular Level
The specific function of SS-31 centers on cardiolipin, a unique lipid found almost exclusively on the inner mitochondrial membrane. Cardiolipin plays an important role in organizing the protein complexes of the electron transport chain (ETC) for efficient energy production. SS-31 is engineered to target and bind to cardiolipin due to its positive charge and specific molecular structure. This interaction stabilizes cardiolipin, preventing oxidative damage and structural disruption of the inner membrane during cellular stress. By maintaining the organization and efficiency of the ETC, SS-31 enhances oxidative phosphorylation, increasing Adenosine Triphosphate (ATP) generation and reducing pathogenic reactive oxygen species (ROS) levels.
Key Disease Targets in Clinical Research
The mechanism of action in stabilizing mitochondrial function has led researchers to investigate SS-31 across a spectrum of diseases linked to cellular energy failure or oxidative stress. A major focus is cardiovascular health, particularly heart failure and ischemia-reperfusion injury following a heart attack, where SS-31 may protect heart muscle cells from damage. Another significant target is chronic kidney disease, as the energy-intensive kidney tubule cells are highly susceptible to mitochondrial damage. SS-31 is also being explored for its neuroprotective effects in neurodegenerative conditions like Alzheimer’s and Parkinson’s disease, and in rare genetic disorders such as Barth Syndrome and primary mitochondrial myopathy.
Understanding Research Dosages
The dosages of SS-31 used in research are highly variable, depending on the specific condition being studied, the route of administration, and whether the trial involves acute or chronic treatment. Because SS-31 is an investigational compound, there are no standardized clinical guidelines for its use outside of controlled studies. Researchers have explored two main routes of administration: intravenous (IV) infusion and subcutaneous (SubQ) injection.
In human trials for acute conditions like myocardial infarction, IV infusion dosages have ranged from a continuous infusion of 0.01 mg/kg/hour to 0.25 mg/kg/hour, typically administered over four hours. For chronic conditions, such as heart failure or primary mitochondrial myopathy, studies often use subcutaneous injection with daily doses ranging from 4 milligrams to 40 milligrams. One study in heart failure patients, for instance, tested daily subcutaneous doses of 4 mg or 40 mg for 28 days.
Examples of Specific Protocols
Investigational protocols for neurodegenerative or cardiovascular conditions have suggested a subcutaneous dose of 0.5 mg to 1 mg per kilogram of body weight daily for four to six weeks. For acute injury models, such as ischemia, an intravenous dose of 2 mg per kilogram administered over one to two hours has been utilized. These dosages are specific to experimental protocols and are not approved therapeutic recommendations, often varying significantly from those used in animal models.
Safety Profile and Regulatory Status
Clinical trials have generally found SS-31 to be well-tolerated across tested dose ranges and administration periods. The safety profile suggests that side effects are typically mild and infrequent. The most commonly reported adverse event is a mild reaction at the injection site, such as redness, itching, or pain, which is common for subcutaneously administered compounds.
Other mild side effects occasionally reported include headache, dizziness, and gastrointestinal issues like flatulence or abdominal pain. The long-term safety profile of SS-31 is not fully established, as most completed clinical trials have involved treatment durations of less than four weeks.
The regulatory status of Elamipretide remains investigational for most indications, meaning it is not commercially available or approved by the U.S. Food and Drug Administration (FDA) for general use. The compound has received Orphan Drug Designation for several rare conditions, including Friedreich’s ataxia and primary mitochondrial myopathy, to encourage further development. Elamipretide was granted accelerated approval for the treatment of Barth syndrome, a rare genetic disorder, under the brand name FORZINITY™.