Fecke Wolfgang, Gianfriddo Marco, Gaviraghi Giovanni, Terstappen Georg C, Heitz Freddy
Siena Biotech S.p.A., Strada del Petriccio e Belriguardo 35, 53100 Siena, Italy.
Drug Discov Today. 2009 May;14(9-10):453-64. doi: 10.1016/j.drudis.2009.02.006. Epub 2009 Feb 25.
Huntington's Disease (HD) is a rare neurodegenerative disease caused by mutation of the huntingtin gene that results in a protein with an expanded stretch of glutamine repeats (polyQ). Knowledge of validated targets is in its infancy, and thus, traditional target-based drug discovery strategies are of limited use. Alternative approaches are needed, and early attempts were aimed at identifying molecules that inhibited the aggregation of polyQ huntingtin fragments. More recently, phenotypic assays were used to find molecules able to reverse some of the pathogenic mechanisms of HD. Such discovery strategies have an impact on the configuration of screening cascades for effective translation of drug candidates toward clinical trials.
亨廷顿舞蹈症（HD）是一种罕见的神经退行性疾病，由亨廷顿基因的突变引起，该突变导致一种含有扩展的谷氨酰胺重复序列（多聚谷氨酰胺）的蛋白质。对已验证靶点的了解尚处于起步阶段，因此，传统的基于靶点的药物发现策略用途有限。需要采用替代方法，早期尝试旨在鉴定抑制多聚谷氨酰胺亨廷顿片段聚集的分子。最近，表型分析被用于寻找能够逆转HD某些致病机制的分子。此类发现策略对筛选级联的配置产生影响，以便将候选药物有效地转化为临床试验。
