Modeling focal cortical dysplasia using cortical organoids: looking for new epilepsy therapies

Abstract

Focal cortical dysplasia (FCD) is a malformation of cortical development and its main clinical manifestation is intractable epilepsy. Despite the considerable progress in diagnosis and surgical therapy, treatment of these patients remains a challenge mainly due to surgical inaccessibility in eloquent cortex areas and the absence of etiology-specific anti-epileptic-drugs (AED). Furthermore, it is unclear how abnormal cortical development can contribute to severe seizure generation in cortical dysplastic tissue. Our main goal in this collaborative research is to establish an in vitro human epilepsy-associated model of type II FCD using cortical organoid to recapitulate cortical development and to speed-up screening and discovery of new candidate drugs for the treatment of this severely epileptogenic cortical malformation, besides to contribute to better understand the nature of the intrinsic epileptogenicity displayed by FCD lesions.