NEUROBIOLOGY OF EPILEPSY GENES

Informations projet

EPITOR

N° de convention de subvention: 682345

DOI

10.3030/682345

Projet clôturé

Date de signature de la CE 27 Septembre 2016

Date de début 1 Octobre 2016

Date de fin 30 Septembre 2022

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 1 998 760,00

Contribution de l’UE

€ 1 998 760,00

Coordonné par

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

Periodic Reporting for period 4 - EPITOR (NEUROBIOLOGY OF EPILEPSY GENES)

Période du rapport: 2021-04-01 au 2022-09-30

Résumé du contexte et des objectifs généraux du projet

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.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

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.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

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).

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