Enzyme replacement and enhancement therapies for lysosomal diseases
Enzyme replacement and enhancement therapies for lysosomal diseases
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DOI：
10.1023/b:boli.0000031101.12838.c6
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发表时间：
2004-01-01
影响因子：
4.2
通讯作者：
Desnick, RJ
中科院分区：
文献类型：
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作者：
Desnick, RJ
尽管 de Duve 于 1964 年首次提出，针对溶酶体贮积病的酶替代疗法 (ERT) 直到 20 世纪 90 年代初才成为现实，当时其安全性和有效性在 1 型戈谢病中得到证实。如今，针对戈谢病、法布里病和 I 型粘多糖贮积症 (MPS I) 的 ERT 已成为现实，针对庞贝病、MPS II 和 MPS VI 的重组人酶临床试验正在进行中，并且即将开始针对内曼-匹克 B 病。除了 ERT 之外，酶增强疗法 (EET) 还提供了一种新的治疗策略来增加突变蛋白的残留功能。 EET 采用小分子作为“药理学伴侣”来拯救错误折叠和/或不稳定的突变酶或具有残留功能的蛋白质。 EET 还提供了治疗神经退行性溶酶体疾病的可能性，因为这些小治疗分子可以穿过血脑屏障。综述了ERT的现状以及EET治疗溶酶体贮积病的前景。
Although first suggested by de Duve in 1964, enzyme replacement therapy (ERT) for lysosomal storage diseases did not become a reality until the early 1990s when its safety and effectiveness were demonstrated in type 1 Gaucher disease. Today, ERT is a reality for Gaucher disease, Fabry disease and mucopolysaccharidosis type I (MPS I), and clinical trials with recombinant human enzymes are ongoing in Pompe disease, MPS II and MPS VI, and are about to begin in Neimann-Pick B disease. In addition to ERT, enzyme enhancement therapy (EET) offers a novel therapeutic strategy to increase the residual function of mutant proteins. EET employs small molecules as 'pharmacological chaperones' to rescue misfolded and/or unstable mutant enzymes or proteins that have residual function. EET also offers the possibility of treating neurodegenerative lysosomal disorders since these small therapeutic molecules may cross the blood-brain barrier. The current status of ERT and the prospects for EET for lysosomal storage diseases are reviewed.