[用于治疗亨廷顿舞蹈症的基因沉默方法]

[Gene silencing approaches for the treatment of Huntington's disease].

作者信息

Merienne Nicolas, Déglon Nicole

机构信息

Lausanne university hospital (CHUV), department of clinical neurosciences (DNC), laboratory of cellular and molecular neurotherapies (LCMN), avenue de Beaumont, Pavillon 3, 1011 Lausanne, Suisse ; Lausanne university hospital (CHUV), neuroscience research center (CRN), LCMN, Lausanne, Suisse.

出版信息

Med Sci (Paris). 2015 Feb;31(2):159-67. doi: 10.1051/medsci/20153102012. Epub 2015 Mar 4.

DOI:10.1051/medsci/20153102012

PMID:25744262

Abstract

Huntington's disease is a rare neurodegenerative disease caused by a pathologic CAG expansion in the exon 1 of the huntingtin (HTT) gene. Aggregation and abnormal function of the mutant HTT (mHTT) cause motor, cognitive and psychiatric symptoms in patients, which lead to death in 15-20 years. Currently, there is no treatment for HD. Experimental approaches based on drug, cell or gene therapy are developed and reach progressively to the clinic. Among them, mHTT silencing using small non-coding nucleic acids display important physiopathological benefit in HD experimental models.

摘要

亨廷顿舞蹈症是一种罕见的神经退行性疾病，由亨廷顿蛋白（HTT）基因外显子1中病理性的CAG重复扩增引起。突变型HTT（mHTT）的聚集和异常功能导致患者出现运动、认知和精神症状，这些症状会在15至20年内导致患者死亡。目前，尚无针对亨廷顿舞蹈症的治疗方法。基于药物、细胞或基因疗法的实验方法正在不断发展，并逐渐进入临床阶段。其中，使用小非编码核酸沉默mHTT在亨廷顿舞蹈症实验模型中显示出重要的生理病理学益处。