Baraban Scott C, Löscher Wolfgang
Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, CA, 94143, USA,
Adv Exp Med Biol. 2014;813:283-94. doi: 10.1007/978-94-017-8914-1_23.
Despite the development of numerous novel antiepileptic drugs (AEDs) in recent years, several unmet clinical needs remain, including resistance to AEDs in about 30 % of patients with epilepsy, adverse effects of AEDs that can reduce quality of life, and the lack of treatments that can prevent development of epilepsy in patients at risk. Animal models of seizures and epilepsy have been instrumental in the discovery and preclinical development of novel AEDs, but obviously the previously used models have failed to identify drugs that address unmet medical needs. Thus, we urgently need fresh ideas for improving preclinical AED development. In this review, a number of promising models will be described, including the use of simple vertebrates such as zebrafish (Danio rerio), large animal models such as the dog and newly characterized rodent models of pharmacoresistant epilepsy. While these strategies, like any animal model approach also have their limitations, they offer hope that new more effective AEDs will be identified in the coming years.
尽管近年来开发了众多新型抗癫痫药物(AEDs),但仍存在一些未满足的临床需求,包括约30%的癫痫患者对AEDs耐药、AEDs的不良反应会降低生活质量,以及缺乏可预防有风险患者发生癫痫的治疗方法。癫痫发作和癫痫的动物模型在新型AEDs的发现和临床前开发中发挥了重要作用,但显然之前使用的模型未能识别出满足未满足医疗需求的药物。因此,我们迫切需要改进临床前AED开发的新思路。在这篇综述中,将描述一些有前景的模型,包括使用斑马鱼(Danio rerio)等简单脊椎动物、犬等大型动物模型以及新鉴定的药物抵抗性癫痫啮齿动物模型。虽然这些策略,与任何动物模型方法一样也有其局限性,但它们为未来几年识别出更新、更有效的AEDs带来了希望。