Intrathecal idursulfase‐ IT in children younger than 3 years with neuronopathic mucopolysaccharidosis II in a single‐arm, open‐label, phase 2/3 substudy and extension
Year: 2026
Type: article
Abstract: Data from a phase 2/3, randomized, controlled, open‐label, multicenter trial in children with neuronopathic mucopolysaccharidosis II (MPS II; Hunter syndrome) older than 3 years suggested a benefit of intrathecal idursulfase‐IT on cognitive functioning in some patients. We describe a separate, parallel, open‐label, single‐arm, 52‐week substudy of the same trial (NCT02055118) that investigated idursulfase‐IT in children with MPS II younger than 3 years at enrollment and Bayley Scales of Infant and Toddler Development (BSID‐III) quotient 55–85. This report describes a prespecified analysis of nine patients (aged 1.4–3.0 years) who had received 3‐years' treatment with idursulfase‐IT. BSID‐III cognitive composite scores generally remained relatively stable over time. At the last available assessment, scores were “high average” (110; n = 1), “average” (100–90; n = 4), and “low average” (85–80; n = 4). Eight patients transitioned to the Differential Ability Scales (DAS‐II) after ages ≥42 months, and scores decreased for all patients when the instrument for assessing cognitive function changed. However, DAS‐II General Conceptual Ability scores were relatively stable for the remainder of the follow‐up. At the last available assessment, scores were “average” (106; n = 1), “low average” (85–80; n = 3), and “very low” (69–43; n = 4). Cerebrospinal fluid concentrations of total glycosaminoglycans were markedly reduced from baseline levels (mean [range] 1278 [429–2660] ng/mL) by week 16 and remained low thereafter. Data suggest early enzyme replacement therapy may stabilize cognitive development or slow the progression of cognitive impairment in young patients with neuronopathic MPS II.
Source: JIMD Reports
DOI: 10.1002/jmd2.12443
Institutions: University of North Carolina at Chapel Hill, Northwestern University, Lurie Children's Hospital, UCSF Benioff Children's Hospital, Hospital Infantil Universitario Niño Jesús, Instituto Nacional de Pediatria, University of Manchester, St Mary's Hospital, Manchester University NHS Foundation Trust, Hospices Civils de Lyon, University of Toronto, Hospital for Sick Children, Women's and Children's Hospital
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,200
Funders: European High Performance Computing Joint Undertaking, Suzhou Key Laboratory of Functional Nano and Soft Materials, Otsuka Pharmaceutical Factory, Houston Endowment, Pfizer, Natural Science Foundation of Shanghai, Aso Group, Natural Science Foundation of Jilin Province, Health and Environmental Sciences Institute, Sveučilište u Zagrebu, Amrita Vishwa Vidyapeetham University, Sunovion, University of Manitoba, Les Laboratories Pierre Fabre, Jed Foundation, SRM Institute of Science and Technology, Shanghai Municipal Health Commission, Universities Federation for Animal Welfare, European Commission, European Centre for Disease Prevention and Control, National Research Foundation, University of Pretoria, Department of Science and Technology, Ministry of Science and Technology, India, Council of Scientific and Industrial Research, India, Indian Council of Agricultural Research, Higher Education Authority, Deutsche Forschungsgemeinschaft, National Natural Science Foundation of China, Ministry of Education of the People's Republic of China, King Saud University, Austrian Science Fund, Imam Mohammed Ibn Saud Islamic University, Carl Tryggers Stiftelse för Vetenskaplig Forskning, Chiang Mai University, China Postdoctoral Science Foundation, Natural Science Foundation of Fujian Province, Science and Technology Commission of Shanghai Municipality, Natural Science Foundation of Guangdong Province, National Research Foundation of Korea, Guangdong Medical Research Foundation, Natural Science Foundation of Hubei Province, Javna Agencija za Raziskovalno Dejavnost RS, Vetenskapsrådet, Kerman University of Medical Sciences, Higher Education Commission, Pakistan, National Cheng Kung University Hospital, Natural Science Foundation of Heilongjiang Province, Kermanshah University of Medical Sciences, Shionogi, Babol University of Medical Sciences, Russian Science Foundation, National University of Sciences and Technology, Ministry of Education and Science of Ukraine, Peking University, Chongqing Municipal Education Commission, Università degli Studi di Udine, Boehringer Ingelheim Stiftung, Council of Science and Technology, U.P., Walailak University, Alzheimer Nederland, State Key Laboratory of Organic–Inorganic Composites, Ministry of Science and Higher Education of the Russian Federation, Priority Academic Program Development of Jiangsu Higher Education Institutions, Collaborative Innovation Center of Suzhou Nano Science and Technology, Higher Education Discipline Innovation Project, Advanced Materials and Bioengineering Research, Fundación Gonzalo Río Arronte, Breakthrough Cancer Research, National Institutes of Health, Directorate for Biological Sciences, Directorate for Engineering, Đại học Quốc gia Hà Nội, Bayer Foundation, Australian Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Science and Engineering Research Board, Chung Shan Medical University Hospital, Korea Institute of Energy Technology Evaluation and Planning, National Key Research and Development Program of China, Institut Lagrange de Paris, Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province, Basic and Applied Basic Research Foundation of Guangdong Province, Student Research Committee, Tabriz University of Medical Sciences, National Institute on Aging, Basic Energy Sciences, Defence and Security Accelerator, Astrophysics Division, HORIZON EUROPE European Research Council, Medical Research Future Fund, Irish Rugby Football Union
OpenAlex ID: W7130935018