Zeiss Caroline J
Section of Comparative Medicine, Yale University School of Medicine, 375 Congress Ave, New Haven, CT 06520, USA.
Drug Discov Today. 2015 Apr;20(4):475-82. doi: 10.1016/j.drudis.2014.10.015. Epub 2014 Nov 4.
For many chronic diseases, translational success using the animal model paradigm has reached an impasse. Using Alzheimer's disease as an example, this review employs a networks-based method to assess repeatability of outcomes across species, by intervention and mechanism. Over 75% of animal studies reported an improved outcome. Strain background was a significant potential confounder. Five percent of interventions had been tested across animals and humans, or examined across three or more animal models. Positive outcomes across species emerged for donepezil, memantine and exercise. Repeatable positive outcomes in animals were identified for the amyloid hypothesis and three additional mechanisms. This approach supports in silico reduction of positive outcomes bias in animal studies.
对于许多慢性疾病而言,采用动物模型范式的转化研究已陷入僵局。以阿尔茨海默病为例,本综述采用基于网络的方法,按干预措施和作用机制评估不同物种间研究结果的可重复性。超过75%的动物研究报告称有改善结果。品系背景是一个显著的潜在混杂因素。5%的干预措施已在动物和人类中进行测试,或在三种或更多动物模型中进行研究。多奈哌齐、美金刚和运动在不同物种间均呈现出阳性结果。针对淀粉样蛋白假说和其他三种作用机制,在动物研究中也发现了可重复的阳性结果。这种方法有助于在计算机模拟中减少动物研究中阳性结果偏差。