The synthetic peptide SS-31, known by the drug name Elamipretide, is a small, water-soluble molecule developed by researchers. It is composed of a short chain of amino acids, specifically D-Arg-dimethylTyr-Lys-Phe-NH2. The purpose of this molecule is to protect and support cellular health by focusing on energy production. Its design allows it to assist cells in maintaining function, a process challenged by aging and various disease states.
The Role of SS-31 in Mitochondrial Function
Within our cells are structures called mitochondria, often referred to as cellular “powerhouses.” Their primary job is to generate the vast majority of the cell’s supply of adenosine triphosphate (ATP), the main molecule for storing and transferring energy. This energy fuels all cellular activities. With age or in certain diseases, the efficiency of mitochondria can decline, leading to reduced energy output and increased damage from oxidative stress.
This decline is often linked to the instability of the inner mitochondrial membrane, where energy production occurs. SS-31 is designed to address this issue by passing through cell membranes and selectively accumulating in mitochondria. This targeting is due to its attraction to a lipid called cardiolipin, found almost exclusively in the inner mitochondrial membrane. Cardiolipin helps organize the proteins of the electron transport chain, the machinery that produces ATP.
When SS-31 binds to cardiolipin, it acts as a stabilizing agent. This interaction helps maintain the structural integrity of the membrane and the arrangement of the energy-producing protein complexes. By doing so, it enhances the efficiency of the electron transport chain, leading to more robust ATP synthesis and a reduction in electron leakage. This leakage is a primary source of reactive oxygen species (ROS), harmful molecules that cause oxidative stress.
Investigated Therapeutic Applications
The action of SS-31 on mitochondria has made it a candidate for treating conditions where cellular energy deficits and oxidative stress are contributing factors. Research has explored its potential in several areas of medicine, connecting mitochondrial health to the function of specific tissues and organs.
An area of investigation is in ophthalmic diseases like dry age-related macular degeneration (AMD) and Leber’s hereditary optic neuropathy (LHON), which involve vision loss from retinal cell death. These cells have high energy demands, and their survival is linked to mitochondrial performance. The ReCLAIM clinical trial evaluated Elamipretide in patients with dry AMD. While it did not meet primary vision improvement goals, it did slow the degradation of a mitochondrial-rich layer of photoreceptors, suggesting a protective effect.
Cardiovascular conditions, particularly heart failure, are another focus. The heart muscle requires a constant supply of ATP to pump blood effectively. In heart failure, mitochondria within cardiac cells become dysfunctional, leading to an energy crisis. While animal studies showed Elamipretide could improve left ventricular function, a human clinical trial did not show a significant improvement in this area, though some quality-of-life metrics trended positively.
Research has also extended to kidney disease, where SS-31 has been studied for its ability to protect against ischemia-reperfusion injury. This damage occurs when blood supply is temporarily cut off and then restored, a problem during organ transplants and certain surgeries. A clinical trial found that Elamipretide administered during stent placement in patients with atherosclerotic renal artery stenosis was associated with improved kidney blood flow and function three months later.
Preliminary research has also touched upon neurodegenerative disorders like Alzheimer’s and Parkinson’s disease, where mitochondrial dysfunction is believed to play a part in neuronal loss. Preclinical studies in animal models have shown that SS-31 can offer neuroprotective effects by preserving mitochondrial function. While promising, this remains an emerging area of study not yet confirmed in human trials.
Administration and Formulation of SS-31
The delivery of peptide-based drugs like SS-31 requires specific methods to ensure they reach their target intact. If taken orally, peptides are broken down by enzymes in the digestive system, rendering them ineffective. For this reason, research on SS-31 has utilized administration routes that bypass the digestive tract.
The most common method used in clinical trials is subcutaneous injection, where the peptide is delivered into the tissue just beneath the skin for slow and sustained absorption. Intravenous infusions have also been used in some clinical settings, providing more direct and rapid delivery into the bloodstream.
To address localized conditions, targeted formulations are also in development. For ophthalmic diseases, researchers have explored using SS-31 as topical eye drops. This method is designed to deliver the peptide directly to the cells of the eye, maximizing its concentration where it is needed most while minimizing systemic exposure.
Clinical Research and Safety Profile
SS-31, under the name Elamipretide, is an investigational drug, meaning it is undergoing testing in clinical trials and is not yet approved by regulatory bodies like the FDA. The clinical development process involves multiple stages to establish effectiveness and safety. Phase 1 trials assess safety, Phase 2 evaluates efficacy and safety, and Phase 3 confirms these findings in a larger population.
Elamipretide has been studied in trials for conditions including primary mitochondrial myopathy and Barth syndrome. While some trials did not meet their primary goals, others have shown encouraging results in specific patient subgroups or on certain secondary measures. For instance, the TAZPOWER trial for Barth syndrome showed improvements in muscle strength and cardiac function, leading to a long-term extension study.
Across these human studies, Elamipretide has generally demonstrated a favorable safety profile, with the majority of reported side effects being mild to moderate. The most frequently observed adverse event is an injection site reaction, such as temporary redness, swelling, or pain. Other less common side effects have included dizziness and headache. Its availability remains limited to participants in clinical trials as researchers continue to gather data.