NEUROBIOLOGY OF EPILEPSY GENES

Informazioni relative al progetto

EPITOR

ID dell’accordo di sovvenzione: 682345

DOI

10.3030/682345

Progetto chiuso

Data della firma CE 27 Settembre 2016

Data di avvio 1 Ottobre 2016

Data di completamento 30 Settembre 2022

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 998 760,00

Contributo UE

€ 1 998 760,00

Coordinato da

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

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

Periodo di rendicontazione: 2021-04-01 al 2022-09-30

Sintesi del contesto e degli obiettivi generali del progetto

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.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

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.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

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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