University of North Carolina at Chapel Hill, Chapel Hill, NC.
Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom.
Genet Med. 2022 Jul;24(7):1437-1448. doi: 10.1016/j.gim.2022.04.002. Epub 2022 May 20.
Intrathecal (IT) idursulfase-IT for the treatment of cognitive impairment is being investigated in pediatric patients with neuronopathic mucopolysaccharidosis II (MPS II) in addition to intravenous idursulfase. In this article, we report the findings for 54 months of idursulfase-IT treatment in an ongoing phase I/II extension trial (NCT01506141).
A total of 15 male participants with neuronopathic MPS II (aged 3-11 years at enrollment) who were previously treated with intravenous idursulfase entered the extension study. Idursulfase-IT 10 mg or 30 mg was administered monthly via an IT drug delivery device or lumbar puncture, if indicated. The primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics, cerebrospinal fluid glycosaminoglycan levels, and cognitive function.
In total, 15 participants received a median (range) of 50 (18-55) idursulfase-IT doses. Idursulfase-IT was generally well tolerated; there were no life-threatening adverse events (AEs) or deaths. Most serious AEs were related to the IT drug delivery device; only 2 serious AEs were related solely to idursulfase-IT. After treatment with idursulfase-IT, cerebrospinal fluid glycosaminoglycans were decreased in all participants; these decreases were maintained. Cognitive function was stabilized in 3 of 4 testable participants at month 55.
These long-term results support the clinical development of idursulfase-IT for patients with MPS II with cognitive impairment.
除了静脉注射伊杜硫酸酶（idursulfase）外，鞘内（IT）伊杜硫酸酶-IT 也被用于治疗神经病变黏多糖贮积症 II 型（MPS II）患者的认知障碍。本文报告了一项正在进行的 I/II 期扩展试验（NCT01506141）中伊杜硫酸酶-IT 治疗 54 个月的结果。
共有 15 名接受过静脉注射伊杜硫酸酶治疗的男性神经病变 MPS II 患者（入组时年龄为 3-11 岁）进入扩展研究。每月通过 IT 药物输送装置或腰椎穿刺给予伊杜硫酸酶-IT 10 mg 或 30 mg，如果需要的话。主要终点是安全性和耐受性；次要终点包括药代动力学、脑脊液糖胺聚糖水平和认知功能。
共有 15 名参与者接受了中位数（范围）为 50（18-55）次伊杜硫酸酶-IT 治疗。伊杜硫酸酶-IT 通常耐受性良好；无危及生命的不良事件（AE）或死亡。大多数严重 AE 与 IT 药物输送装置有关；仅有 2 例严重 AE 仅与伊杜硫酸酶-IT 有关。接受伊杜硫酸酶-IT 治疗后，所有参与者的脑脊液糖胺聚糖均减少；这些减少得以维持。在 55 个月时，4 名可测试参与者中有 3 名的认知功能稳定。
这些长期结果支持伊杜硫酸酶-IT 用于治疗认知障碍的 MPS II 患者的临床开发。
