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

促进局灶性和全身性癫痫发生的表观遗传光合机制 (EpiGENet)

• 批准号: 194375904
• 负责人: Professor Dr. Albert Becker
• 金额: --
• 依托单位: Institut für Pharmakologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/194375904?language=en
• 关键词: Epigenetic; phatomechanisms; promoting; epileptogenesis; focal

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.

大约有1%的人患有癫痫，大约有1%的人患有癫痫。30%的患者对目前可用的抗癫痫药物治疗缺乏反应。然而，在受影响的患者中，自发性耐药癫痫发作活动的发作和进展仍然难以预测和确定，无论其致癫痫性状况如何，即，创伤性脑损伤、颞叶（海马）硬化或遗传。本CRP的目的是表征癫痫发生的常见表观遗传病理机制，从而确定药物治疗的新靶点。来自癫痫患者的实验动物模型和充分表征的样品将可用于全基因组关联研究、甲基化组的大规模平行测序和基因表达分析。这些有价值的数据库的生物信息学整合将有助于阐明候选癫痫发生基因（CEG）和改变CEG表达的共同性状。我们的CRP包括不同方法学方法的专业知识，即遗传平台技术，动物模型和人体样本的功能和分子研究。我们的6个IP和3个AP之间将组织高度可见的互动和协作，以交换数据和样本池。此外，将向联盟提供专业知识，以验证常见癫痫形式中的异常表观遗传调控模式。这些结果将引导我们进行转译研究，解决表观遗传药物治疗或shRNA干扰的临床前试验。连续视频EEG监测将阐明两种策略对临床相关动物模型中慢性癫痫的医学衰减或预防进展的影响。该CRP由来自6个欧洲国家和澳大利亚的9个实验室组成，在癫痫模型和人类样本的遗传和功能研究方面具有长期的跟踪记录。它还促进欧洲癫痫脑库，该库为欧洲各国的科学研究提供标准化的人脑标本。我们的CRP目标的新奇和所有申请人的专业知识将产生明确的结果。