Photopharmacology as novel treatment option for refractory focal epilepsies

The application of photopharmacology with the aim of treating epileptic seizures is unique and has never been done before. Photopharmacology is a highly novel approach that combines smart drug design with the implantation of an optic fibre in the seizure focus in order to obtain precise, spatiotemporal control of a therapeutic effect. Since the technique does not require the brain tissue to be genetically altered, it might become superior to opto- and chemogenetics. I propose a pioneering proof-of-principle study in mice for the application of photoswitchable cannabinoids for treating focal seizures. Both the rising evidence supporting their anticonvulsant properties in treatment-resistant epilepsies and my access to exclusive and potent photoswitchable cannabinoids were considered when choosing cannabinoids as the treatment option. At the beginning of my in vivo experiments preliminary data resulting from in vitro electrophysiology in slices will be available. I will study the anticonvulsant effects of the photoswitchable cannabinoids in acute mouse seizure models and in a well-validated epilepsy model with recurrent refractory seizures. I will also examine the effects of
the photoswitchable cannabinoids on motor and memory dysfunction. My hypothesis is that these photoswitchable ligands will have a reduced side effect profile while still maintaining their anticonvulsive properties.