Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK.
Nat Rev Drug Discov. 2018 Feb;17(2):133-150. doi: 10.1038/nrd.2017.214. Epub 2017 Nov 17.
Lysosomal storage disorders (LSDs) - designated as 'orphan' diseases - are inborn errors of metabolism caused by defects in genes that encode proteins involved in various aspects of lysosomal homeostasis. For many years, LSDs were viewed as unattractive targets for the development of therapies owing to their low prevalence. However, the development and success of the first commercial biologic therapy for an LSD - enzyme replacement therapy for type 1 Gaucher disease - coupled with regulatory incentives rapidly catalysed commercial interest in therapeutically targeting LSDs. Despite ongoing challenges, various therapeutic strategies for LSDs now exist, with many agents approved, undergoing clinical trials or in preclinical development.
溶酶体贮积症（LSDs）——被指定为“孤儿”疾病——是由编码参与溶酶体动态平衡各个方面的蛋白质的基因突变引起的先天性代谢缺陷。多年来，由于 LSDs 的发病率较低，它们一直被视为开发疗法的不具吸引力的靶点。然而，首个 LSD 的商业化生物治疗方法——1 型 Gaucher 病的酶替代疗法的开发和成功，加上监管激励措施，迅速激发了治疗 LSD 的商业兴趣。尽管仍面临挑战，但目前已有多种 LSD 的治疗策略，许多药物已获得批准、正在进行临床试验或处于临床前开发阶段。
