Activity-dependent antioxidant gene therapy protects against epileptogenesis

Epilepsy affects >50 million people worldwide, and nearly one-third are drug resistant. Current antiseizure medications primarily provide symptomatic seizure control but do not effectively modify the underlying disease process or halt the progression of epilepsy 1 . Oxidative stress can be both a cause and a consequence of seizures, yet constitutive antioxidant therapy interferes with physiological redox signaling 2 . Here, we developed an activity-dependent gene therapy that couples Nrf2, a transcription factor and upstream modulator of antioxidant responses 3 , to cfos , an immediate-early gene promoter selectively induced in hyperactive neurons 4 .