Project 462082

Epilepsy is a common and debilitating neurological condition, characterized by frequent seizures due to abnormal electrical activity in the brain. Although many drugs are available for epilepsy management, as many as 30% of patients with epilepsy are resistant to current drugs, and others suffer significant side effects. Also surprisingly, many of the drugs used to treat epilepsy are decades (or even centuries) old. Taken together, these observations suggest that new approaches are needed. Our study will focus on a new class of anti-epileptic drugs called potassium channel openers. The protoype drug in this class is retigabine, and is unique because it is the only anti-epileptic drug that targets a class of protein called voltage-gated potassium channels in the brain. These voltage-gated channels alter their activity when the drug binds, helping to suppress seizures. Our study applies several cutting edge approaches to study the specific chemical forces that allow potassium channel activators to interact with their target, along with a simple test for effectiveness using a fish model. This allows us to tailor drugs with specific features, and potentially accelerate development of this new drug class. We anticipate that our research project will identify changes that can be made to improve the potency and effectiveness of potassium channel activators.