Epigenetic phatomechanisms promoting epileptogenesis in focal and generallized epilepsies (EpiGENet)

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About 1% of the population has epilepsy, and approx. 30% of the patients lack response to currently available antiepileptic drug treatment. Onset and progression of spontaneous drug-resistant seizure activity remains, however, difficult to predict and determine in affected patients, irrespective of their epileptogenic condition, i.e., traumatic brain injury, temporal lobe (hippocampal) sclerosis or genetic inheritance. The objective of this CRP is to characterize common epigenetic pathomechanisms of epileptogenesis and, thereby, to identify novel targets for pharmacotherapy. Experimental animal models and well-characterized samples from epilepsy patients will be available for genome wide association studies, massive parallel sequencing of the methylome and gene expression analysis. Bioinformatic integration of these valuable data pools will help to elucidate candidate epileptogenesis genes (CEG) and common traits for altered CEG expression. Our CRP comprises expertise in different methodological approaches, i.e. genetic platform technologies, functional and molecular studies in animal models and human samples. Highly visible interaction and collaboration will be organized between our 6 IPs and 3 APs to exchange data and sample pools. In addition, specialized expertise will be made available to the consortium to validate aberrant epigenetic regulation patterns in common forms of epilepsies. These results will lead us to translational studies addressing preclinical trials for epigenetic drug treatment or shRNA interference. Continuous video-EEG monitoring will clarify the impact of either strategy to medically attenuate or prevent the progression of chronic epilepsy in clinically relevant animal models. This CRP consists of 9 laboratories from 6 European countries and Australia with a long-standing track record in genetic and functional research in both epilepsy models and human samples. It also promotes the European Epilepsy Brain Bank, which provides standardized human brain specimens for scientific research across European countries. The novelty of our CRP objectives and published expertise of all applicants will generate definitive results.