Howland David S, Munoz-Sanjuan Ignacio
CHDI Management/CHDI Foundation, Princeton, New Jersey, USA.
Mov Disord. 2014 Sep 15;29(11):1397-403. doi: 10.1002/mds.26008. Epub 2014 Aug 22.
Unraveling the pathophysiology and testing candidate therapeutics in neurodegenerative disorders is, necessarily, highly dependent on model systems. Because Huntington's disease (HD) is caused by a single (expanded CAG tract) mutation in the huntingtin (HTT) gene, a richness of model systems, particularly mice, have been engineered to both dissect disease mechanisms and test potential therapeutics. Even so, as with other neurodegenerative diseases, very little success has been achieved in translating HD mouse model drug testing results to the clinic. Because of the considerable costs-human, opportunity, and financial-there is a pressing need to improve the use of existing HD models and also to develop models in higher species beyond rodent, such as sheep, minipig, and nonhuman primate, to bridge the translational gap from preclinical to clinical testing of candidate therapeutics.
揭示神经退行性疾病的病理生理学并测试候选治疗方法必然高度依赖模型系统。由于亨廷顿舞蹈症（HD）是由亨廷顿蛋白（HTT）基因中的单个（CAG重复序列扩增）突变引起的，因此已经构建了丰富的模型系统，尤其是小鼠模型，用于剖析疾病机制和测试潜在的治疗方法。即便如此，与其他神经退行性疾病一样，将HD小鼠模型药物测试结果转化到临床方面取得的成功非常有限。鉴于人力、机会和资金等方面的巨大成本，迫切需要改进现有HD模型的使用，并开发啮齿动物以外的高等物种模型，如绵羊、小型猪和非人类灵长类动物，以弥合候选治疗方法从临床前测试到临床试验的转化差距。
