University of Münster, Department of Neurology, Albert-Schweitzer-Campus 1, Gebäude A1, 48149 Münster, Germany.
Expert Opin Emerg Drugs. 2013 Jun;18(2):109-20. doi: 10.1517/14728214.2013.790363. Epub 2013 Apr 19.
Neuroprotection aims to restrict the ischaemic damage following stroke by preventing salvageable neurons from dying. Despite successes in experimental stroke studies, neuroprotective strategies have failed in clinical trials so far. Nevertheless, promising neuroprotective drugs are currently being investigated in clinical trials.
This review provides an overview of the existing treatment of acute ischaemic stroke, discusses current research goals and puts special emphasis on emerging neuroprotective drugs. The authors systematically searched the database Clinicaltrials.gov for ongoing Phase II and Phase III clinical trials of neuroprotective drugs for acute ischaemic stroke. Mechanisms of action of these candidate neuroprotectants and the results of preceding preclinical studies and clinical pilot trials are described.
In order to facilitate a successful translation from bench to bedside, future experimental studies should follow rigorous quality standards. Recent concepts to overcome the translation roadblock include the implementation of multicentre preclinical Phase III studies, the use of stroke models in non-human primates and the introduction of a preclinical trial registration.
神经保护旨在通过防止可挽救的神经元死亡来限制中风后的缺血性损伤。尽管在实验性中风研究中取得了成功,但迄今为止,神经保护策略在临床试验中均告失败。然而,目前正在临床试验中研究有前途的神经保护药物。
本综述提供了对急性缺血性中风现有治疗方法的概述,讨论了当前的研究目标,并特别强调了新兴的神经保护药物。作者系统地在数据库 Clinicaltrials.gov 中搜索了正在进行的急性缺血性中风神经保护药物的 II 期和 III 期临床试验。描述了这些候选神经保护剂的作用机制以及之前的临床前研究和临床初步试验的结果。
为了促进从实验室到临床的成功转化,未来的实验研究应遵循严格的质量标准。克服转化障碍的最新概念包括实施多中心临床前 III 期研究、在非人类灵长类动物中使用中风模型以及引入临床前试验注册。