Muenzer Joseph, Burton Barbara K, Harmatz Paul, Gutiérrez-Solana Luis González, Ruiz-Garcia Matilde, Jones Simon A, Guffon Nathalie, Inbar-Feigenberg Michal, Bratkovic Drago, Rust Stewart, Hale Michael, Wu Yuna, Yee Karen S, Whiteman David A H, Alexanderian David
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
J Inherit Metab Dis. 2025 May;48(3):e12790. doi: 10.1002/jimd.12790. Epub 2024 Sep 9.
Mucopolysaccharidosis II (MPS II; Hunter syndrome; OMIM 309900) is a rare, X-linked, heterogeneous lysosomal storage disease. Approximately two-thirds of patients develop cognitive impairment, which is difficult to assess in clinical trials, partly owing to the variable nature of cognitive impairment. Analyzing data from siblings can help to minimize this heterogeneity. We report analyses of cognitive function from siblings with MPS II enrolled in clinical trials: a natural history study (NCT01822184), a randomized, open-label, phase 2/3 study of intravenous (IV) idursulfase with or without intrathecal idursulfase (idursulfase-IT; NCT02055118), and its extension (NCT2412787). Cognitive function was assessed using Differential Abilities Scales, Second Edition General Conceptual Ability (DAS-II GCA) scores; Bayley Scales of Infant and Toddler Development, Third Edition; and Vineland Adaptive Behavior Scales, Second Edition Adaptive Behavior Composite (VABS-II ABC). Seven sets of siblings (six pairs and one set of three) were included. All patients received IV idursulfase and 10 received subsequent idursulfase-IT. Younger siblings initiated IV idursulfase at an earlier age than their older sibling(s) in six of the sets; the younger sibling started treatment before 1 year of age in three sets. Monthly idursulfase-IT was generally associated with a stabilization of cognitive function: DAS-II GCA and VABS-II ABC scores were higher at age-matched assessments in the majority of those who either received idursulfase-IT earlier than their sibling or who received idursulfase-IT versus no idursulfase-IT. These data suggest that early initiation of intrathecal enzyme replacement therapy may stabilize or slow cognitive decline in some patients with neuronopathic MPS II.
黏多糖贮积症II型（MPS II；亨特综合征；OMIM 309900）是一种罕见的X连锁、异质性溶酶体贮积病。大约三分之二的患者会出现认知障碍，这在临床试验中很难评估，部分原因是认知障碍的性质多变。分析来自兄弟姐妹的数据有助于最小化这种异质性。我们报告了参与临床试验的MPS II型兄弟姐妹的认知功能分析：一项自然史研究（NCT01822184）、一项静脉注射（IV）艾度硫酸酯酶联合或不联合鞘内注射艾度硫酸酯酶（艾度硫酸酯酶-IT；NCT02055118）的随机、开放标签2/3期研究及其扩展研究（NCT2412787）。使用差异能力量表第二版一般概念能力（DAS-II GCA）评分、贝利婴幼儿发展量表第三版以及文兰适应行为量表第二版适应行为综合（VABS-II ABC）对认知功能进行评估。纳入了七组兄弟姐妹（六对和一组三人）。所有患者均接受静脉注射艾度硫酸酯酶，10名患者随后接受鞘内注射艾度硫酸酯酶。在其中六组中，年幼的兄弟姐妹开始静脉注射艾度硫酸酯酶的年龄比其年长的兄弟姐妹更早；在三组中，年幼的兄弟姐妹在1岁之前开始治疗。每月进行鞘内注射艾度硫酸酯酶通常与认知功能的稳定相关：在大多数比其兄弟姐妹更早接受艾度硫酸酯酶-IT治疗或接受了艾度硫酸酯酶-IT治疗而非未接受治疗的患者中，年龄匹配评估时的DAS-II GCA和VABS-II ABC评分更高。这些数据表明，早期开始鞘内酶替代疗法可能会稳定或减缓一些神经病变型MPS II患者的认知衰退。
