Stealth BioTherapeutics develops elamipretide, a mitochondrially targeted peptide that appears to improve mitochondrial function in older individuals. Mitochondria are the power plants of the cell, producing the chemical energy store molecule ATP to power cellular operations. Mitochondria falter with age, however, negatively affecting tissue function throughout the body.
Here, researchers note a short term gain in ATP production following elamipretide infusion. The results in detail make it clear that individual responses are highly variable, but the average settles down to a statistically significant 27% gain. Like other present approaches to improving mitochondrial function (e.g. various forms of NAD+ upregulation), demonstrating improved tissue function as a result of biochemical differences of this nature remains a challenge. Muscle function did not show compelling improvement in this study.
Loss of mitochondrial function contributes to fatigue, exercise intolerance, and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial.
Non-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling at rest. The first dorsal interosseous (FDI) muscle was studied in 39 healthy older adult subjects (60 to 85 yrs of age; 46% female) who were enrolled based on the presence of poorly functioning mitochondria. We measured volitional fatigue resistance by force-time integral over repetitive muscle contractions.
A single ELAM dose elevated mitochondrial energetic capacity in vivo relative to placebo immediately after a 2-hour infusion. No difference was found on day 7 after treatment, which is consistent with the half-life of ELAM in human blood. No significant changes were found in resting muscle mitochondrial coupling. Despite the increase in ATPmax there was no significant effect of treatment on fatigue resistance in the FDI.
These results highlight that ELAM rapidly and reversibly elevates mitochondrial capacity after a single dose. This response represents the first demonstration of a pharmacological intervention that can reverse mitochondrial dysfunction in vivo immediately after treatment in aging human muscle.