Cullman Chemoprotection Center members Drs. Dinkova-Kostova and Dayalan Naidu participated in a fascinating study recently published in the journal Brain, showing that increasing the body’s antioxidant defenses was protective against epilepsy in an animal model. They tested this novel strategy to increase endogenous antioxidant defenses using RTA 408, a drug synthesized by Reata Pharmaceuticals that is already in clinical trials for other indications. RTA 408 inhibited reactive oxygen species production, mitochondrial depolarization and cell death in a cell culture model of seizure-like activity. RTA 408 given after status epilepticus in vivo increased ATP, prevented neuronal death, and dramatically reduced (by 94%) the frequency of late spontaneous seizures for at least 4 months following status epilepticus. This mechanism of producing a neuroprotective and disease-modifying effect, supports the hypothesis that mitochondrial dysfunction and reactive oxygen species generation is a key event in the development of epilepsy.
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