Elamipretide

Elamipretide is a mitochondrial cardiolipin binder that localizes to the inner mitochondrial membrane to improve mitochondrial morphology and function. Elamipretide was shown to attenuate neuronal oxidative stress and neuroinflammation, activate neural mitochondrial biogenesis, enhance mitochondrial respiration, and protect against neural apoptosis. Protective effects of elamipretide against neuronal loss and inflammation have been reported in traumatic brain injury, hind limb ischemia–reperfusion injury, type II diabetes, and spinal cord injury. Clinically significant QTc interval prolongation was not observed at three times the peak concentration of the maximum recommended dose.

Barth syndrome is a rare X-linked genetic disorder characterized by mitochondrial dysfunction. Elamipretide is a mitochondrial cardiolipin binder that penetrates cells and accumulates in the mitochondria: It localizes to the inner mitochondrial membrane, improving mitochondrial morphology and function. Elamipretide's mechanism of action involves electrostatic interactions with cardiolipin, a phospholipid critical for mitochondrial structure and electron transport chain function. By binding to cardiolipin, elamipretide stabilizes the mitochondrial membrane, prevents oxidative damage, and maintains membrane potential. This interaction preserves cristae integrity, reduces reactive oxygen species (ROS) production, and maintains ATP production. Elamipretide also enhances the activity of mitochondrial respiratory complexes, facilitating efficient electron transfer and ATP synthesis. Furthermore, elamipretide inhibits the opening of the mitochondrial permeability transition pore (mPTP), protecting against mitochondrial damage during reperfusion and reducing cell death in ischemic conditions.