Approximately 65 million people worldwide have epilepsy. Although certain brain injuries are known to predispose to epilepsy, there are no treatments that reduce this risk. We have found that an important cellular signaling pathway, the JAK/STAT pathway, is activated after brain injuries that lead to epilepsy, and that inhibiting this activation reduces subsequent seizure frequency in an animal model. The proposed studies will examine novel JAK/STAT inhibitors with the ultimate goal of identifying those with optimal chemical properties that obtain high brain concentrations, effectively inhibit JAK/STAT activation after injury, have low toxicity and are most efficacious in reducing or preventing seizures and/or cognitive co-morbidities in an animal model of acquired epilepsy. We expect to identify lead JAK/STAT inhibitors that can be advanced towards clinical testing to prevent or inhibit development of acquired epilepsy following brain injury.
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