Epigenetic pathomechanisms promoting epileptogenesis in focal and generalized epilepsies (EpiGENet)
About 1% of the population has epilepsy, and 30% of the patients lack response to currently available antiepileptic drugs. Onset and progression of drug‐resistant seizures remain, however, difficult to predict in affected patients, irrespective of their epileptogenic condition. The objective of this CRP is to characterize common epigenetic pathomechanisms of epileptogenesis. Epigenetic mechanisms are self‐perpetuating, posttranslational modifications of nuclear proteins, and DNA that can produce lasting alterations in chromatin structure and gene expression patterns. Results will be obtained from animal models and human brain specimens using advanced experimental tools, and will help to identify novel targets for pharmacotherapy in these difficult-to-treat patients.
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Picture: Epigenetic chromatin modifications regulate gene expression. The methylation hypothesis proposes that seizures can change the epigenetic chromatin state. Abbreviations: Acetyl- (Acetylation); AED (antiepileptic drug); C-G (CpG dinucleotide); DNMT (DNAmethyltransferase); HDAC (histone deacetylase); MeCP2 (methyl CpG binding protein 2); Methylation 4 (CH3).
PROJECT LEADER:
Professor Asla Pitkänen, Epilepsy Research Laboratory, Department of Neurobiology, University of Eastern Finland, Kuopio, Finland
PRINCIPAL INVESTIGATORS:
Professor Albert Becker, Department of Neuropathology, Bonn University, Germany
Professor Ingmar Blümcke, Department of Neuropathology, University Hospital Erlangen, Germany
Dr Katarzyna Lukasiuk, Laboratory of Epileptogenesis, Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Warsaw, Poland
Dr Thomas Sander, Cologne Center for Genomics, University of Cologne, Germany
Professor Günther Sperk, Department of Pharmacology, Medical University Innsbruck, Austria
ASSOCIATED PARTNERS:
Dr Christophe Bernard, INSERM UMR 751, University Aix Marseille, France
Associate Professor Assam El-Osta, BakerIDI Heart & Diabetes Institute, Melbourne, Australia
Professor Sanjay Sisodiya, Department of Clinical & Experimental Epilepsy, Institute of Neurology, University College London, United Kingdom
