Periodic Reporting for period 4 - EPITOR (NEUROBIOLOGY OF EPILEPSY GENES)
Período documentado: 2021-04-01 hasta 2022-09-30
Focal Cortical Dysplasia (FCDs) are malformations of the brain cortical development which manifest with childhood-onset epilepsy and for which treatment often requires epilepsy surgery to control seizures. Nowadays, in the evolving epilepsy surgery population, FCDs represent a growing proportion and thus bring crucial challenges for patient care and treatment.
The project's objectives are to elucidate the genetic etiology of these disorders, decipher the underlying molecular and cellular pathogenic mechanisms using brain tissue obtained from epilepsy surgery and preclinical mouse model, and set up targeted therapeutic strategies.
The project's objectives are to elucidate the genetic etiology of these disorders, decipher the underlying molecular and cellular pathogenic mechanisms using brain tissue obtained from epilepsy surgery and preclinical mouse model, and set up targeted therapeutic strategies.
The research project investigates the genetic etiology of focal epilepsies, particularly those associated with Focal Cortical Dysplasia (FCD). The research team has shown that FCDs are caused by brain somatic mutations in genes belonging to the mTOR signaling pathway that occur during brain development. We were able to elucidate the genetic etiology of 30% of FCD1 patients and 60% of FCD2 patients by panel sequencing.
We have generated preclinical mouse models of somatic mutations in DEPDC5 and MTOR genes that recapitulate the main features of the pathology i.e. spontaneous seizures and neuropathological abnormalities.
We have generated preclinical mouse models of somatic mutations in DEPDC5 and MTOR genes that recapitulate the main features of the pathology i.e. spontaneous seizures and neuropathological abnormalities.
We discovered the presence of specific features only present in cells carrying the mutations in human FCD brain tissues. We generated preliminary data using molecules administered to preclinical FCD mice that open an exciting therapeutic perspective to treat refractory childhood epilepsies (ERC PoC EpiSen).