Activity-dependent gene therapy for epilepsy

Epilepsy is a family of neurological disorders affecting 1% of the general population.

About 30% of patients are resistant to current medications, and surgical treatment options are possible for only a minority of selected cases.

Pharmacoresistant patients continue to experience seizures throughout their lifetime, with a severe impact on their quality of life.

The development of novel and more effective treatment strategies is therefore highly needed, as well as preventive approaches that could block the progression of the disease.The main objective of the current proposal is to develop highly specific and precise gene therapy approaches that target critical cell populations involved in the development of epilepsy and seizures.

By using a combination of advanced molecular biology, electrophysiological and imaging techniques, we will (i) identify hyper-active neuronal ensembles involved in the early stages of epileptogenesis, (ii) charachterise their location, molecular identity and functional alterations, (iii) apply gene therapy approaches designed to limit the functional output of hyper-active neurons and prevent the development of chronic epilepsy.

These approaches will be validated in different animal models of epilepsy, and will provide important new knowledge on the mechanisms of epileptogenesis, as well as basis for the development of preventive treatments that could further be translated in the human condition.