Kim Tae-Wan
Department of Pathology and Cell Biology, and Taub Institute of Research on Alzheimer's Disease and the Aging Brain, Columbia University Medical Center, New York, NY, 10032, USA,
Neurotherapeutics. 2015 Jan;12(1):132-42. doi: 10.1007/s13311-014-0325-7.
Alzheimer's disease (AD) is the most common cause of dementia and represents one of the highest unmet needs in medicine today. Drug development efforts for AD have been encumbered by largely unsuccessful clinical trials in the last decade. Drug repositioning, a process of discovering a new therapeutic use for existing drugs or drug candidates, is an attractive and timely drug development strategy especially for AD. Compared with traditional de novo drug development, time and cost are reduced as the safety and pharmacokinetic properties of most repositioning candidates have already been determined. A majority of drug repositioning efforts for AD have been based on positive clinical or epidemiological observations or in vivo efficacy found in mouse models of AD. More systematic, multidisciplinary approaches will further facilitate drug repositioning for AD. Some experimental approaches include unbiased phenotypic screening using the library of available drug collections in physiologically relevant model systems (e.g. stem cell-derived neurons or glial cells), computational prediction and selection approaches that leverage the accumulating data resulting from RNA expression profiles, and genome-wide association studies. This review will summarize several notable strategies and representative examples of drug repositioning for AD.
阿尔茨海默病（AD）是痴呆症最常见的病因，也是当今医学领域尚未满足的最大需求之一。在过去十年中，AD的药物研发工作因临床试验大多未成功而受阻。药物重新定位，即发现现有药物或候选药物新治疗用途的过程，是一种具有吸引力且适时的药物研发策略，尤其适用于AD。与传统的从头开始药物研发相比，由于大多数重新定位候选药物的安全性和药代动力学特性已经确定，因此时间和成本都有所降低。AD的大多数药物重新定位工作都是基于积极的临床或流行病学观察结果，或者是在AD小鼠模型中发现的体内疗效。更系统、多学科的方法将进一步促进AD的药物重新定位。一些实验方法包括在生理相关模型系统（如干细胞衍生的神经元或神经胶质细胞）中使用可用药物库进行无偏表型筛选、利用RNA表达谱积累数据的计算预测和选择方法，以及全基因组关联研究。本综述将总结AD药物重新定位的几种显著策略和代表性实例。
