Development of a novel anti-neuroinflammatory experimental therapeutic for epilepsy and Alzheimer's risk

The overall goal is to evaluate the effect of MW189 in the Scn1a+/- genetic epilepsy mouse model, including effects on seizure frequency and severity, survival and cognition following a first-hit hyperthermia-induced seizure event. a. Phase I - We will validate preliminary seizure and survival efficacy in Scn1a+/- mice by extending to a fully powered dataset; and determine the time course of cytokine production following an initial hyperthermia-induced seizure in this model. This will aid in determining the treatment window for efficacy studies in Phase II. b. Phase II - We will determine the effect of daily MW189 treatment on epilepsy endpoints over the course of 12 days following an initial hyperthermia-induced seizure in Scn1a+/- mice using video-EEG analysis. This will include testing at least 3 doses (plus vehicle), and 2 intervention delays following the hyperthermia-induced seizure. In addition, we will evaluate the effect of MW189 treatment on cognitive performance following an initial hyperthermia-induced seizure in a separate cohort Scn1a+/- mice. This will include testing at a single dose (plus vehicle) and one delay, based on the optimal window/dose for seizure endpoints.