The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), a CWOW proposal in response to RFA-NS-16-012, is designed to facilitate the development of antiepileptogenic therapies by removing barriers and promoting large-scale collaborative research efforts by multidisciplinary teams of basic and clinical neuroscientists with access to extensive patient populations, well-defined and rigidly standardized animal models, and cutting-edge analytic methodology. We focus our proposal on antiepileptogenesis in post- traumatic epilepsy (PTE) following traumatic brain injury (TBI), as this condition offers the best opportunity to determine the time of onset of the epileptogenic process in patients. The EpiBioS4Rx Scientific Premise is: Epileptogenesis after TBI can be prevented with specific treatments; the identification of relevant biomarkers and performance of rigorous preclinical trials will permit the future design and performance of economically feasible full-scale clinical trials of antiepileptogenic therapies. Based on the work from a P20 planning grant, our program will consist of the following: (1) identify biomarkers of epileptogenesis in our animal model and in patients, (2) Develop and utilize a standardized platform for preclinical trials of potential antiepileptogenic (AEG) drugs, (3) Identify 1 or more lead antiepileptogenic drugs for a future interventional clinical trial, (4) Establish a network of advanced TBI centers capable of carrying out future clinical trials featuring our lead antiepileptogenic drugs used in the context of a personalized, medicine-based approach utilizing our panel of biomarkers, and (5) Develop and incorporate a public engagement program involving the mutual education and collaboration of consumers, consumer organizations and professionals to design and execute future large-scale interventional clinical trials of antiepileptogenic therapies.

Public Health Relevance

Despite decades of research that have led to an understanding of many causes of epilepsy and yielded over fifteen new antiseizure drugs and novel non-drug therapies, there remain no treatments that prevent epilepsy, nor are there ways to identify and prove such treatments. A major obstacle to research in this area is the fact that studies from single institutions are inadequate to answer the most important questions. The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is a proposal for a large, international, multicenter Center without Walls (CWOW) to address this pressing need by using studies of animals and patients with traumatic brain injury (TBI) leading to post-traumatic epilepsy (PTE), to develop the techniques and patient populations necessary to carry out future cost effective full-scale clinical trials of epilepsy prevention therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS100064-03
Application #
9650648
Study Section
Special Emphasis Panel (ZNS1)
Program Officer
Churn, Severn Borden
Project Start
2017-01-15
Project End
2021-11-30
Budget Start
2018-12-01
Budget End
2019-11-30
Support Year
3
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of Southern California
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Hernan, Amanda E; Schevon, Catherine A; Worrell, Gregory A et al. (2017) Methodological standards and functional correlates of depth in vivo electrophysiological recordings in control rodents. A TASK1-WG3 report of the AES/ILAE Translational Task Force of the ILAE. Epilepsia 58 Suppl 4:28-39
Fisher, Robert S; Cross, J Helen; French, Jacqueline A et al. (2017) Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology. Epilepsia 58:522-530
Nariai, Hiroki; Beal, Jules; Galanopoulou, Aristea S et al. (2017) Scalp EEG Ictal gamma and beta activity during infantile spasms: Evidence of focality. Epilepsia 58:882-892

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