Noh H, Lee J I
Department of Pharmacy, College of Pharmacy, Yonsei University, Incheon, Korea; Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, Korea.
J Clin Pharm Ther. 2014 Jun;39(3):215-24. doi: 10.1111/jcpt.12136. Epub 2014 Feb 25.
Mucopolysaccharidoses (MPSs) are a group of rare inherited metabolic diseases caused by genetic defects in the production of lysosomal enzymes. MPSs are clinically heterogeneous and are characterized by progressive deterioration in visceral, skeletal and neurological functions. This article aims to review the classification and pathophysiology of MPSs and discuss current therapies and new targeted agents under development.
A Medline search through PubMed was performed for relevant articles and treatment guidelines on MPSs published in English for years 1970 to September of 2013 inclusive. The references listed in the identified articles, prescribing information of the drugs approved for the treatment of MPSs, as well as recent clinical trial information posted on Clinicaltrials.gov website, were reviewed.
Until recently, supportive care was the only option available for the management of MPSs. In the early 2000s, enzyme replacement therapy (ERT) was approved by the United States Food and Drug Administration (FDA) for the treatment of MPS I, II and VI. Clinical trials of ERT showed substantial improvements in patients' somatic symptoms; however, no benefit was found in the neurological symptoms because the enzymes do not readily cross the blood-brain barrier (BBB). Haematopoietic stem cell transplantation (HSCT), another potentially curative treatment, is not routinely advocated in clinical practice due to its high risk profile and lack of evidence for efficacy, except in preserving cognition and prolonging survival in young patients with severe MPS I. In recent years, substrate reduction therapy (SRT) and gene therapy have been rapidly gaining greater recognition as potential therapeutic avenues.
Enzyme replacement therapy (ERT) is effective for the treatment of many somatic symptoms, particularly walking ability and respiratory function, and remains the mainstay of MPS treatment. The usefulness of HSCT has not been established adequately for most MPSs. Although still under investigation, SRT and gene therapy are promising MPS treatments that may prevent the neurodegeneration not affected by ERT.
黏多糖贮积症（MPSs）是一组由溶酶体酶产生的基因缺陷引起的罕见遗传性代谢疾病。MPSs在临床上具有异质性，其特征是内脏、骨骼和神经功能进行性恶化。本文旨在综述MPSs的分类和病理生理学，并讨论当前的治疗方法以及正在研发的新型靶向药物。
通过PubMed对1970年至2013年9月期间以英文发表的关于MPSs的相关文章和治疗指南进行了Medline检索。对已识别文章中列出的参考文献、已批准用于治疗MPSs的药物的处方信息以及Clinicaltrials.gov网站上发布的近期临床试验信息进行了综述。
直到最近，支持性护理仍是MPSs治疗的唯一选择。21世纪初，酶替代疗法（ERT）被美国食品药品监督管理局（FDA）批准用于治疗MPS I、II和VI。ERT的临床试验显示患者的躯体症状有显著改善；然而，在神经症状方面未发现益处，因为这些酶不易穿过血脑屏障（BBB）。造血干细胞移植（HSCT）是另一种潜在的治愈性治疗方法，但由于其高风险以及缺乏疗效证据，在临床实践中并不常规提倡，除了在保留严重MPS I年轻患者的认知和延长生存期方面。近年来，底物减少疗法（SRT）和基因疗法作为潜在的治疗途径迅速获得了更多认可。
酶替代疗法（ERT）对治疗许多躯体症状有效，特别是行走能力和呼吸功能，并且仍然是MPS治疗的主要手段。对于大多数MPSs，HSCT的有效性尚未得到充分证实。尽管仍在研究中，但SRT和基因疗法是有前景的MPS治疗方法，可能预防不受ERT影响的神经退行性变。
