Improve Mitochondrial Function & Reduce Oxidative Stress
Elamipretide
Children’s Hospital of Philadelphia
Phase I/II
Elamipretide (aka Bendavia, MPT-131, and SS31) is a tetrapeptide compound being developed by Stealth Therapeutics. It targets the inner mitochondrial membrane where it binds reversibly to cardiolipin. In preclinical or clinical studies, elamipretide increases mitochondrial respiration, improves electron transport chain function and ATP production, and reduces formation of pathogenic reactive oxygen species (ROS) levels. Functional benefit is achieved through improvement of ATP production as well as interruption and potential reversal of damaging oxidative stress.
HOW DOES A DRUG GET DEVELOPED?
Stages of Development for Elamipretide
The drug development process can be thought of as a series of stages, and successful drugs must pass through each stage to become available to patients.
Elamipretide came out of a chance discovery of a family of compounds (Szeto–Schiller (SS) peptides) that selectively target the mitochondrial ETC to optimize efficiency of electron transport and restore cellular bioenergetics in aging and diverse disease models without any effect on the normal healthy organism. Originally named SS-31 (also named MTP-131 and Bendavia) it entered clinical development for a variety of complex diseases. Studies in isolated mitochondria and cells demonstrated that elamipretide improved electron transport, decreased mitochondrial generation of reactive oxygen species and elevated ATP generation.
In mouse experiments, treatment with elamipretide prevented the increase in mitochondrial oxidative stress and muscle wasting associated with disuse atrophy in hindlimb and diaphragm. In aging mice, a single IP injection of elamipretide increased ATP, levels, oxidative phosphorylation, and reduced muscle fatigue Longer term treatment with elamipretide demonstrated similar increases in mitochondrial energetics and decreases in muscle fatigue
Stealth BioTherapeutics obtained regulatory approval for the first in human studies with elamipretide (then known as MTP-131). The first trials in 2015 were small, open label phase I trials in other diseases. The regulatory filings for the FA Investigator Initiated Study (IIS) With Elamipretide were in 2021.
The Children’s Hospital of Philadelphia (CHOP) has a Phase 1/2 clinical trial studying the safety and efficacy of Elamipretide in the treatment of advanced stage FRDA symptoms, specifically vision loss and cardiac disease in both adults and older children. This study is completely enrolled and results are anticipated in the second half of 2024.