Translational platform for epilepsy therapy and biomarker discovery

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PROJECT SUMMARY There is currently no validated treatment to prevent the development of acquired epilepsies, such as post- traumatic epilepsy. The availability of biomarker that predicts, at an early stage, people at risk to develop epilepsy and benefit from treatment interventions would significantly accelerate and de-risk the process of identifying an antiepileptogenic therapy. In this study, that is based on collaborations and preliminary data derived from EpiBioS4Rx, an NINDS funded Center without Walls, we aim to create a rigorous and effective preclinical model to screen a new candidate treatment to prevent posttraumatic epilepsy in the lateral fluid percussion injury model as well as identify biomarkers to guide treatment implementation. We will follow a multicenter, double-blinded, vehicle-controlled, randomized preclinical antiepileptogenesis study following the high standards of rigor advocated by NINDS, the AES/ILAE Translational Research Task Force and the ARRIVE guidelines. We have formed a collaborative group of four international preclinical testing centers (Albert Einstein College of Medicine, University of Melbourne, two UCLA sites), supported by experts in pharmacokinetic modeling (University of Minnesota), protein biomarker research (Uniformed Services University of the Health Services) and bioinformatics (University of Southern California). We plan to test a compound that removes pathological iron stores from the brain and test whether it can modify early biomarkers of epileptogenesis and injury. We aim to identify (a) at least one panel of multimodal biomarkers that can predict early on treatment response to the iron chelator, including the development of post-traumatic epileptogenesis, (b) at least one biomarker of epileptogenesis, (c) and determine whether iron chelator treatment can prevent post-traumatic epilepsy development.