Immusoft Corp., Seattle, WA 98103, USA.
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
Biomolecules. 2021 Jan 29;11(2):189. doi: 10.3390/biom11020189.
Mucopolysaccharidosis type I (MPS I) is a lysosomal disease, caused by a deficiency of the enzyme alpha-L-iduronidase (IDUA). IDUA catalyzes the degradation of the glycosaminoglycans dermatan and heparan sulfate (DS and HS, respectively). Lack of the enzyme leads to pathologic accumulation of undegraded HS and DS with subsequent disease manifestations in multiple organs. The disease can be divided into severe (Hurler syndrome) and attenuated (Hurler-Scheie, Scheie) forms. Currently approved treatments consist of enzyme replacement therapy (ERT) and/or hematopoietic stem cell transplantation (HSCT). Patients with attenuated disease are often treated with ERT alone, while the recommended therapy for patients with Hurler syndrome consists of HSCT. While these treatments significantly improve disease manifestations and prolong life, a considerable burden of disease remains. Notably, treatment can partially prevent, but not significantly improve, clinical manifestations, necessitating early diagnosis of disease and commencement of treatment. This review discusses these standard therapies and their impact on common disease manifestations in patients with MPS I. Where relevant, results of animal models of MPS I will be included. Finally, we highlight alternative and emerging treatments for the most common disease manifestations.
黏多糖贮积症 I 型（MPS I）是一种溶酶体疾病，由α-L-艾杜糖苷酸酶（IDUA）缺乏引起。IDUA 催化糖胺聚糖硫酸皮肤素和硫酸乙酰肝素（分别为 DS 和 HS）的降解。缺乏该酶会导致未降解的 HS 和 DS 病理性积累，随后在多个器官出现疾病表现。该疾病可分为严重型（Hurler 综合征）和轻度型（Hurler-Scheie、Scheie 型）。目前批准的治疗方法包括酶替代疗法（ERT）和/或造血干细胞移植（HSCT）。轻度型疾病患者通常单独接受 ERT 治疗，而 Hurler 综合征患者的推荐治疗方法为 HSCT。虽然这些治疗方法显著改善了疾病表现并延长了生命，但仍存在相当大的疾病负担。值得注意的是，治疗可以部分预防，但不能显著改善临床症状，因此需要早期诊断疾病并开始治疗。本文讨论了这些标准治疗方法及其对 MPS I 患者常见疾病表现的影响。在相关情况下，还将包括 MPS I 动物模型的结果。最后，我们强调了针对最常见疾病表现的替代和新兴治疗方法。
