Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK.
Geoffrey Jefferson Brain Research Centre, the Manchester Academic Health Science Centre, Northern Care Alliance & University of Manchester, Manchester, UK.
Expert Opin Drug Discov. 2022 Jun;17(6):559-568. doi: 10.1080/17460441.2022.2072828. Epub 2022 May 23.
The global health burden of stroke is significant and few therapeutic treatment options currently exist for patients. Pre-clinical research relies heavily on rodent stroke models but the limitations associated with using these systems alone has meant translation of drug compounds to the clinic has not been greatly successful to date. Zebrafish disease modeling offers a potentially complementary platform for pre-clinical compound screening to aid the drug discovery process for translational stroke research.
In this review, the authors introduce stroke and describe the issues associated with the current pre-clinical drug development pipeline and the advantages that zebrafish disease modeling can offer. Existing zebrafish models of ischemic and hemorrhagic stroke are reviewed. Examples of how zebrafish models have been utilized for drug discovery in other disease disciplines are also discussed.
Zebrafish disease modeling holds the capacity and potential to significantly enhance the stroke drug development pipeline. However, for this system to be more widely accepted and incorporated into translational stroke research, continued improvement of the existing zebrafish stroke models, as well as focussed collaboration between zebrafish and stroke researchers, is essential.
卒中给全球带来了沉重的健康负担,但目前患者的治疗选择非常有限。临床前研究严重依赖于啮齿动物卒中模型,但这些系统本身存在的局限性意味着,迄今为止,药物化合物向临床的转化并没有取得很大的成功。斑马鱼疾病模型为临床前化合物筛选提供了一个潜在的互补平台,有助于转化性卒中研究的药物发现过程。
在这篇综述中,作者介绍了卒中,并描述了当前临床前药物开发管道相关的问题,以及斑马鱼疾病模型可以提供的优势。回顾了现有的斑马鱼缺血性和出血性卒中模型。还讨论了斑马鱼模型如何在其他疾病学科的药物发现中得到利用的例子。
斑马鱼疾病模型具有显著增强卒中药物开发管道的能力和潜力。然而,为了使该系统得到更广泛的接受并纳入转化性卒中研究,必须持续改进现有的斑马鱼卒中模型,并在斑马鱼和卒中研究人员之间进行重点合作。