King's College London, Wolfson Centre of Age-Related Diseases , London SE1 1UL , UK.
Expert Opin Pharmacother. 2014 Sep;15(13):1797-810. doi: 10.1517/14656566.2014.936848. Epub 2014 Jul 3.
Alzheimer's disease (AD), Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) together account for the vast majority of individuals with dementia. Approximately 35 million people worldwide are affected with this condition, and despite decades of research, effective therapies that slow or reverse disease progression have not yet been developed. The recent failure of several large-scale clinical trials is beginning to challenge the magnitude of focus on amyloid-related therapies for AD, and newer drug targets that have shown promise in the laboratory are being investigated in clinical trials.
This review summarises the current understanding of the underlying biology of AD, PDD and DLB and outlines the most recent drug candidates in advanced clinical trials.
The lack of success in drug discovery for disease-modifying therapies for AD, PDD and DLB can be attributed to limitations in the design of clinical trials and the narrow focus of molecular targets for treatment. New avenues for drug discovery including repositioning and novel target identification may now provide opportunities for success, provided a critical mass of clinical trials is achieved through increased investment.
阿尔茨海默病（AD）、帕金森病痴呆（PDD）和路易体痴呆（DLB）合在一起占痴呆症患者的绝大多数。全球约有 3500 万人受到这种疾病的影响，尽管已经进行了数十年的研究，但仍未开发出能够减缓或逆转疾病进展的有效疗法。最近几项大型临床试验的失败开始挑战人们对 AD 相关淀粉样蛋白治疗的重视程度，并且实验室中显示出前景的更新药物靶点正在临床试验中进行研究。
本文综述了 AD、PDD 和 DLB 潜在生物学的最新认识，并概述了目前处于临床后期试验阶段的最新候选药物。
AD、PDD 和 DLB 疾病修饰治疗的药物发现缺乏成功，可以归因于临床试验设计的局限性和治疗分子靶点的狭隘关注。通过增加投资实现临床试验的大量投入，重新定位和新的靶点识别等药物发现的新途径可能为成功提供机会。
