摘要
肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)尚无有效的治疗方法,目前已经发现多个致病基因以及修饰基因可导致ALS。反义寡核苷酸(antisense oligonucleotides,ASOs)是可以调节目的mRNA的分子工具,可以针对ALS的突变基因进行治疗。本文综述ASOs在ALS治疗中研究进展,从治疗机制、研究情况等方面进行总结,目前针对超氧化物歧化酶基因1(superoxide dismutase 1,SOD1)、反式激活反应-DNA-结合蛋白(transactive response DNA binding protein,TARDBP)、9号染色体开放阅读框72(chromosome 9 open reading frame 72,C9ORF72)、肉瘤融合基因(fused in sarcoma,FUS)的ASOs在动物实验中得到其有效的结果,多项临床试验正在进行,但在药物体内分布、药物用量把控、ALS不同类型适用性等方面的问题尚待解决,以研制出减缓疾病进展且副作用小的ASOs。
Amyotrophic lateral sclerosis(ALS)is a neurodegenerative disease,and there is no effective treatment.Multiple pathogenic genes and modified genes have been found to cause ALS.Antisense oligonucleotide(ASOs)are molecular tools that can not only regulate target mRNA but also be used to treat mutant genes of ALS.This article will review the progress of research on the treatment of common genes in ALS using ASOs,including their therapeutic mechanisms and research processes.At present,ASOs targeting the SOD1 gene,TARDBP gene,C9ORF72 gene,and FUS gene have achieved effective results in animal experiments,and multiple clinical trials are ongoing.However,problems in drug distribution in vivo,drug dosage control,and applicability of different types of ALS still need to be solved.Therefore,it is urgent to develop ASOs that can slow down disease progression with minimal side effects.
作者
何中慧
张莹
姜宏佺
HE Zhonghui;ZHANG Ying;JIANG Hongquan(Department of Neurology,the First Affiliated Hospital of Harbin Medical University,Harbin 150001,China.)
出处
《中国神经精神疾病杂志》
CAS
CSCD
北大核心
2023年第5期291-295,共5页
Chinese Journal of Nervous and Mental Diseases
基金
国家自然科学基金青年科学基金(编号:81601102)
黑龙江省自然科学基金优秀青年项目(编号:YQ2020H013)
黑龙江省博士后启动基金(编号:LBH-Q19128)
中国初级卫生保健基金会(编号:2022HX034)。
