Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA.
Neuropharmacology. 2020 May 1;167:107702. doi: 10.1016/j.neuropharm.2019.107702. Epub 2019 Jul 10.
The epilepsies are a complex group of disorders that can be caused by a myriad of genetic and acquired factors. As such, identifying interventions that will prevent development of epilepsy, as well as cure the disorder once established, will require a multifaceted approach. Here we discuss the progress in scientific discovery propelling us towards this goal, including identification of genetic risk factors and big data approaches that integrate clinical and molecular 'omics' datasets to identify common pathophysiological signatures and biomarkers. We discuss the many animal and cellular models of epilepsy, what they have taught us about pathophysiology, and the cutting edge cellular, optogenetic, chemogenetic and anti-seizure drug screening approaches that are being used to find new cures in these models. Finally, we reflect on the work that still needs to be done towards identify at-risk individuals early, targeting and stopping epileptogenesis, and optimizing promising treatment approaches. Ultimately, developing and implementing cures for epilepsy will require a coordinated and immense effort from clinicians and basic scientists, as well as industry, and should always be guided by the needs of individuals affected by epilepsy and their families. This article is part of the special issue entitled 'New Epilepsy Therapies for the 21st Century - From Antiseizure Drugs to Prevention, Modification and Cure of Epilepsy'.
癫痫是一组复杂的疾病，可能由多种遗传和获得性因素引起。因此，要确定可以预防癫痫发作的干预措施，以及一旦癫痫发作可以治愈该疾病的方法，就需要采取多方面的方法。在这里，我们讨论推动我们向这一目标前进的科学发现进展，包括鉴定遗传风险因素和大数据方法，这些方法整合了临床和分子“组学”数据集，以确定常见的病理生理特征和生物标志物。我们讨论了许多癫痫动物和细胞模型，它们让我们了解了病理生理学，以及用于在这些模型中寻找新治疗方法的前沿细胞、光遗传学、化学遗传学和抗癫痫药物筛选方法。最后，我们反思了仍然需要做的工作，以便早期识别风险个体，靶向和阻止癫痫发生，并优化有前途的治疗方法。最终，开发和实施癫痫治疗方法需要临床医生和基础科学家、行业的协调和巨大努力，并且应该始终以受癫痫影响的个人及其家庭的需求为指导。本文是题为“21 世纪的新癫痫治疗方法——从抗癫痫药物到癫痫的预防、干预和治疗”的特刊的一部分。
