Gene therapy with precision targeting for epilepsy

The epilepsies affect 1% of population (over 60 million people) worldwide. About 30% of people with epilepsy are resistant to current anti-epilepsy drugs. The annual cost of epilepsy in Europe is estimated at 15 B€.

Epilepsy is a major unmet health care need that justifies efforts in developing novel treatment strategies, particularly  for drug-resistant population.The main objective of the present proposal is to investigate novel precise gene therapy approaches to enable future clinical applications.

This entails gaining more understanding in fundamental mechanisms of epileptogenesis and inctogenesis, and development of next generation gene therapy, beyond the state-of-the-art, by combinatorial, cell-population specific gene expression strategies which became possible due to recent technological advances in viral vector and molecular biology techniques.We will investigate targeting specific therapeutic genes selectively (i) to excitatory and inhibitory neurons and (ii) to those neuronal ensembles that initiate seizures to normalise hyper-excitability of epileptic network in the brain and achieve superior control of seizure activity, in the latter case, with minimal impact on normal brain function; (iii) Novel gene therapy approaches will be validated in human drug-resistant epileptic tissue obtained by surgical resection from patients, and (iv) first-in-man clinical trial with gene therapy in patients with drug-resistant epilepsy will be perform in the nearest future.