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.
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.
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| Katsarou, Anna-Maria; Galanopoulou, Aristea S; Moshé, Solomon L (2018) Epileptogenesis in neonatal brain. Semin Fetal Neonatal Med 23:159-167 |
| Mazarati, Andrey; Jones, Nigel C; Galanopoulou, Aristea S et al. (2018) A companion to the preclinical common data elements on neurobehavioral comorbidities of epilepsy: a report of the TASK3 behavior working group of the ILAE/AES Joint Translational Task Force. Epilepsia Open 3:24-52 |
| Duncan, Dominique; Vespa, Paul; Toga, Arthur W (2018) DETECTING FEATURES OF EPILEPTOGENESIS IN EEG AFTER TBI USING UNSUPERVISED DIFFUSION COMPONENT ANALYSIS. Discrete Continuous Dyn Syst Ser B 23:161-172 |
| Vespa, Paul M; Shrestha, Vikesh; Abend, Nicholas et al. (2018) The epilepsy bioinformatics study for anti-epileptogenic therapy (EpiBioS4Rx) clinical biomarker: Study design and protocol. Neurobiol Dis : |
| Engel Jr, Jerome (2018) Epileptogenesis, traumatic brain injury, and biomarkers. Neurobiol Dis : |
| Correa, Daniel J; Kwon, Churl-Su; Connors, Susan et al. (2018) Applying participatory action research in traumatic brain injury studies to prevent post-traumatic epilepsy. Neurobiol Dis : |
| Vakharia, Vejay N; Duncan, John S; Witt, Juri-Alexander et al. (2018) Getting the best outcomes from epilepsy surgery. Ann Neurol 83:676-690 |
| Engel Jr, Jerome; Bragin, Anatol; Staba, Richard (2018) Nonictal EEG biomarkers for diagnosis and treatment. Epilepsia Open 3:120-126 |
| Engel Jr, Jerome (2018) The current place of epilepsy surgery. Curr Opin Neurol 31:192-197 |
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