UCLA Department of Neurology, Neurobiology, and Psychiatry & Behavioral Sciences and the Brain Research Institute, David Geffen School of Medicine at UCLA, USA.
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FIN-70211, Kuopio, Finland.
Neuropharmacology. 2020 May 1;167:107735. doi: 10.1016/j.neuropharm.2019.107735. Epub 2019 Aug 1.
There are no pharmacological interventions to prevent the development of epilepsy, although many promising compounds have been identified in the animal laboratory. Clinical trials to validate their effectiveness, however, would currently be prohibitively expensive due to the large subject population and duration of follow-up necessary. There is, therefore, the need to identify biomarkers of epileptogenesis that could identify patients at high risk for epilepsy following a potential epileptogenic insult to enrich the subject population, as well as biomarkers that could determine the effectiveness of therapeutic intervention without the need to wait for seizures to occur. Putative biomarkers under investigation for epileptogenesis and its treatment include genetic, molecular, cellular, imaging, and electrophysiological measures that might reliably predict the development or progression of an epileptic condition, the effects of antiepileptogenic treatment, or cure after surgery. To be clinically useful for most purposes, ideal biomarkers should be noninvasive, and it is anticipated that a profile of multiple biomarkers will likely be required. Ongoing animal research involves a number of experimental models of epileptogenesis, with traumatic brain injury, offering the best potential for translational clinical investigations. Collaborative and multicenter research efforts by multidisciplinary teams of basic and clinical neuroscientists with access to robust, well-defined animal models, extensive patient populations, standardized protocols, and cutting-edge analytical methodologies are likely to be most successful. Such biomarker research should also provide insights into fundamental neuronal mechanisms of epileptogenesis suggesting novel targets for antiepileptogenic treatments. 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'.
目前尚无预防癫痫发生的药理学干预措施，尽管在动物实验室中已经确定了许多有前途的化合物。然而，由于需要大量的研究对象和随访时间，目前进行验证其有效性的临床试验将非常昂贵。因此，有必要确定癫痫发生的生物标志物，以便能够在潜在的致癫痫损伤后识别出癫痫高风险患者，从而丰富研究对象群体；还需要确定生物标志物，以便能够在无需等待癫痫发作的情况下确定治疗干预的效果。正在研究的癫痫发生及其治疗的候选生物标志物包括遗传、分子、细胞、成像和电生理测量，这些测量可能能够可靠地预测癫痫状态的发展或进展、抗癫痫治疗的效果或手术后的治愈。为了在大多数情况下具有临床实用性，理想的生物标志物应该是非侵入性的，预计可能需要多种生物标志物的组合。目前正在进行的动物研究涉及多种癫痫发生的实验模型，其中创伤性脑损伤为转化临床研究提供了最佳的潜在可能性。具有丰富的、定义明确的动物模型、广泛的患者群体、标准化方案和先进的分析方法的基础和临床神经科学家的多学科团队的合作和多中心研究工作可能最成功。此类生物标志物研究还应深入了解癫痫发生的基本神经元机制，为抗癫痫治疗提供新的靶点。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、修饰和治愈”的特刊的一部分。
