An antisense strategy and network pharmacology approach in zebrafish models to identify novel targets for pharmacoresistant epilepsy

The discovery of novel drug targets is a significant challenge in drug development. Specifically, in the field of epilepsy still 30% of patients do not experience adequate seizure control with currently available medications, which highlights the need to look for new approaches capable of defining specific molecular targets that could be used to identify novel anti-epileptic drugs (AEDs). Network-based strategies in drug discovery and development propose to harness the power of biological networks to uncover relationships between drugs, diseaserelated genes, therapeutic targets and diseases, and have been successfully applied to find novel drug targets. In this project, we aim to find new druggable epilepsy targets by combining for the first time a network-based approach and morpholino technology (targeting RNA of interest resulting in a gene knockdown) with zebrafish pharmacoresistant epilepsy models. After a pre-selection of possible targets with transcriptome analysis, a morpholino screen will allow to verify the presumed targets by knocking down their genes. Afterwards, the found targets will be further validated using various techniques. Knowing the target(s) would reveal new biological insights into pathogenic mechanisms leading to pharmacoresistant epilepsies that would enable to screen for new AEDs for this debilitating disorder.