Centre de Recherche du Centre Hospitalier de l'Université de Montréal (N.V.),Montreal Neurological Institute (A.H.,P.H.), and Department of Neurology and Neurosurgery, McGill University (P.H.), Montreal, Quebec, Canada.
Centre de Recherche du Centre Hospitalier de l'Université de Montréal (N.V.),Montreal Neurological Institute (A.H.,P.H.), and Department of Neurology and Neurosurgery, McGill University (P.H.), Montreal, Quebec, Canada
J Pharmacol Exp Ther. 2018 May;365(2):379-397. doi: 10.1124/jpet.117.247171. Epub 2018 Mar 9.
The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate is the gold-standard animal model of Parkinson disease (PD) and has been used to assess the effectiveness of experimental drugs on dyskinesia, parkinsonism, and psychosis. Three species have been used in most studies-the macaque, marmoset, and squirrel monkey-the last much less so than the first two species; however, the predictive value of each species at forecasting clinical efficacy, or lack thereof, is poorly documented. Here, we have reviewed all the published literature detailing pharmacologic studies that assessed the effects of experimental drugs on dyskinesia, parkinsonism, and psychosis in each of these species and have calculated their predictive value of success and failure at the clinical level. We found that, for dyskinesia, the macaque has a positive predictive value of 87.5% and a false-positive rate of 38.1%, whereas the marmoset has a positive predictive value of 76.9% and a false-positive rate of 15.6%. For parkinsonism, the macaque has a positive predictive value of 68.2% and a false-positive rate of 44.4%, whereas the marmoset has a positive predictive value of 86.9% and a false-positive rate of 41.7%. No drug that alleviates psychosis in the clinic has shown efficacy at doing so in the macaque, whereas the marmoset has 100% positive predictive value. The small number of studies conducted in the squirrel monkey precluded us from calculating its predictive efficacy. We hope our results will help in the design of pharmacologic experiments and will facilitate the drug discovery and development process in PD.
1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）损伤的灵长类动物是帕金森病（PD）的金标准动物模型，已被用于评估实验药物对运动障碍、帕金森病和精神病的疗效。在大多数研究中使用了三种物种——猕猴、狨猴和松鼠猴——后两种比前两种使用得少得多；然而，每种物种在预测临床疗效或缺乏疗效方面的预测价值记录很差。在这里，我们回顾了所有已发表的文献，详细描述了评估实验药物对这些物种运动障碍、帕金森病和精神病影响的药理学研究，并计算了它们在临床水平上成功和失败的预测价值。我们发现，对于运动障碍，猕猴的阳性预测值为 87.5%，假阳性率为 38.1%，而狨猴的阳性预测值为 76.9%，假阳性率为 15.6%。对于帕金森病，猕猴的阳性预测值为 68.2%，假阳性率为 44.4%，而狨猴的阳性预测值为 86.9%，假阳性率为 41.7%。在临床上缓解精神病的药物在猕猴中没有显示出疗效，而在狨猴中则有 100%的阳性预测值。在松鼠猴中进行的研究数量较少，我们无法计算其预测疗效。我们希望我们的结果将有助于药理学实验的设计，并将促进 PD 的药物发现和开发过程。
