The road towards precision therapy for genetic epilepsies

Epilepsy is characterized by recurrent seizures and affects 50-70 million people worldwide, of which a third do not become seizure free with currently available drugs. Most current drugs are found serendipitously and despite great advances in the number of treatment options, individual treatment of people with epilepsy is currently largely trial-and-error. Many forms of epilepsy are highly heritable, in particular generalized epilepsies, suggesting that genetics could aid understanding of the pathophysiology, which might enable precision therapy aimed at the underlying cause of epilepsy. Here we describe a broad range of research techniques aimed to improve and personalize treatment of genetic epilepsies. Using large-scale genome-wide association studies, we discovered a large number of epilepsy risk variants that collectively explain much of epilepsy liability. We employed a range of methods to pinpoint the most likely implicated genes and biological processes, which we used to find drugs that target this genetic basis of epilepsy. We further assessed whether genetics could aid diagnosis or predict treatment outcomes for people with epilepsy. Finally, we created prediction models based on clinical variables that could be used to personalize treatment and counselling of people with juvenile myoclonic epilepsy, the most common form of genetic epilepsy. We hope that these findings aid to pave the road towards precision therapy of genetic epilepsies.