Molecular characterization of early infantile epileptic encephalopathy (EIEE) related HCN1 mutations: advancing therapeutics and treatment

Early infantile epileptic encephalopathy (EIEE) is a severe form of epilepsy that affects newborn children. It can be caused by a mutation in a single gene, HCN1, that promotes abnormal neuronal activity leading to epileptic seizures. EIEE patients do not respond to conventional anti-epileptic medications and likely require drugs that specifically target HCN1 proteins. To date, the only HCN-specific drug available on the market is ivabradine, prescribed for heart failure. We propose to advance the treatment of HCN1-EIEE patients by restoring proper HCN1 function with novel therapeutic agents developed in our lab. This includes peptide drugs, monoclonal antibody and molecules under development in academia and industry. We operate in the frame of a large consortium that groups together geneticists, neuroscientists, chemists, clinicians and patients in a collaborative effort to study HCN1-based EIEE. The study will be conducted at all levels, from the atomic structure of the HCN1 protein, to the cellular level of patients-derived neurons to the in vivo level transgenic mice reproducing the HCN1-EIEE patient phenotype. We have obtained positive results already that are worth investigating further.