溶酶体贮积症及其治疗性替代酶类药物研究进展  

Research advances on lysosomal storage diseases and the therapeutic replacement enzymes

作　　者：杨可沁 曹筠嵩 马兰 杨燕 王伟[1] YANG Ke-qin;CAO Yun-song;MA Lan;YANG Yan;WANG Wei(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,NHC Key Laboratory of Biosynthesis of Natural Products,Institute of Materia Medica,Chinese Academy of Medical Sciences,Beijing 100050,China)

机构地区：[1]中国医学科学院药物研究所天然药物活性物质与功能国家重点实验室/国家卫生健康委员会天然药物生物合成重点实验室,北京100050

出　　处：《中国新药杂志》2024年第23期2476-2481,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金资助项目(82073757);中国医学科学院医学与健康科技创新工程资助项目(2021-I2M-1-029,CAMS-2017-I2M-1-011)。

摘　　要：溶酶体贮积症是由于体内溶酶体酶活性降低或丧失造成其作用底物在体内蓄积,进而导致机体多器官病变的一类疾病。目前已有报道的溶酶体贮积症约70余种,涉及多种溶酶体酶缺陷。溶酶体贮积症的治疗包括酶替代疗法、小分子药物疗法(底物减少疗法和分子伴侣等)以及基因疗法。其中应用最广泛的是酶替代疗法,即通过静脉注射的方式补充体内所缺失的溶酶体酶。截至目前共有19种治疗溶酶体贮积症的替代酶类药物经美国FDA批准上市。本文将对常见的溶酶体贮积症、已上市和在研的替代酶类药物等方面进行研究总结,旨在为此类药物的研发提供理论和实验借鉴。Lysosomal storage disorder(LSD)is a multi-organ dysfunction caused by the functional deficit of lysosomal hydrolases,resulting in their substrate storage in organs.More than 70 LSDs have been reported up to now,involving the deficiency of multiple lysosomal hydrolases.Several kind of LSDs can be treated with approved,disease-specific therapies based on enzyme replacement therapy(ERT),small molecules(substrate reduction therapies and chaperones)therapy and gene therapy,among which the most widely applied therapy is the enzyme replacement therapy,characterized by supplying deficient enzymes through intravenous injection.Now there have been 19 ERT agents for LSD approved by United States FDA.This review aims to give a brief introduction on some common lysosomal storage disorders with the corresponding ERT drugs,and the drugs under development in clinical trials.

关 键 词：溶酶体贮积症 酶替代疗法 重组蛋白 生物制剂 糖基化工程 

分 类 号：R961[医药卫生—药理学]