ANR - A new project for the Human Neurogenetics team

Early onset epileptic encephalopathies (EOEE) are intractable and devastating epileptic syndromes. A significant proportion of cases are caused by de novo variants in the KCNQ2 gene, encoding a subunit of the M channel, controling neuronal excitability. Our proposed investigations at the clinical and molecular levels will help decipher the pathophysiological mechanisms and test therapeutic strategies. We bring into the project one of the largest cohort of EOEE patients, a unique knock-in mouse model and human neurones derived from patients' iPS cells. These resources will be used to investigate motor and cognitive phenotypes in human and mouse, and provide a detailed characterization using electrophysiology and omics strategies. We will take advantage of the complementary expertise of the consortium members (MMG, INMED Inserm U1249, INT CNRS UMR 7289, i-Stem, AP-HM) in a translational perspective and will test therapeutic interventions either using candidate drugs or via an unbiased high throughput screening strategy using human neurones. The coordinator is MMG (Human Neurogenetics team) and the project started in october 2019.