SS-31

Enhancing Mitochondrial Function

Primary mitochondrial diseases (PMDs) are prevalent inherited conditions stemming from mitochondrial energy production dysfunction. Symptoms vary but frequently affect high-energy-demand organs like the nervous system, heart, and kidneys. Muscle issues and exercise intolerance are common, with symptoms including fatigue, exercise intolerance, and seizures.

Mitochondrial diseases, especially PMDs, are characterized by disruptions in ATP (adenosine triphosphate) production, which is vital for cellular functions. Efforts to stabilize ATP production in mitochondrial diseases have been ongoing. The development of SS-31 offers promising prospects for achieving this goal.

Initial animal studies demonstrated that SS-31 could restore ATP production in PMDs. Rats with kidney ischemia-perfusion injury, a non-genetic cause of mitochondrial disease, were administered SS-31, resulting in kidney protection, accelerated ATP recovery, and reduced cell damage. Subsequent mouse studies revealed that SS-31 interacted with cardiolipin in mitochondria’s inner membrane and mitigated mitochondrial disease symptoms, regardless of the cause. It also showed potential in addressing age-related mitochondrial dysfunction. These findings led to SS-31 receiving orphan drug status from the FDA and advancing to clinical trials.

In phase II human trials, SS-31 improved exercise performance within just five days of treatment, with no significant safety concerns or adverse effects. However, phase III trials did not provide strong evidence of SS-31’s clinical effectiveness. Some experts believe that the trial endpoints may have been inappropriate, and further research could lead to SS-31’s approval for specific mitochondrial conditions. Dr. Bruce Cohen, director of the Neurodevelopment Science Center at Akron Children’s Hospital, emphasized the encouraging results of prior phase II trials and the need for continued investigation. Other pharmaceutical companies are also showing interest in SS-31 research, planning trials for SS-31 derivatives and exploring alternative treatment endpoints.

Currently, SS-31 is undergoing testing for various human diseases and across different trial models. It is considered safe for human use and can be prescribed under compassionate care exceptions to patients with no other treatment options. While SS-31 is on its way to becoming a mainstream medical treatment for various conditions, it is already accessible to those in need during ongoing clinical trials.

Addressing Ischemia

SS-31 holds significant promise as a treatment for heart failure, a condition known to negatively impact mitochondrial function and exacerbate the disease’s progression. Research conducted on human heart tissue treated with SS-31 demonstrates marked improvements in mitochondrial oxygen flux and the activity of specific ATP production components. Interestingly, this study did not involve cardiolipin restructuring, suggesting that SS-31 might have an alternative mechanism of action on mitochondrial function that warrants further exploration. Several studies have replicated this finding, reinforcing the idea that SS-31’s benefits extend beyond ATP production via cardiolipin interaction. Researchers are actively investigating its ability to modulate the production of reactive oxygen species and enhance mitochondrial function in both acute and chronic scenarios.

Studies involving dogs with advanced heart failure have shown that chronic SS-31 treatment can enhance left ventricular function. Measures of mitochondrial respiration and maximum ATP synthesis correlated with overall improvement in left ventricular function, suggesting that SS-31 could be a valuable long-term treatment for enhancing energy dynamics and reducing cardiac remodeling in advanced heart failure.

Trials exploring SS-31’s use in ST-segment elevation myocardial infarction (heart attack) have found that it can significantly reduce levels of HtrA2, a marker of cardiomyocyte apoptosis. These results indicate that SS-31 may be beneficial in acute heart attacks by reducing injury extent and preserving cardiac tissue.