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Intrathecal idursulfase-IT in children younger than 3 years with neuronopathic mucopolysaccharidosis II in a
Joseph Muenzer1, Barbara K Burton2, Paul Harmatz3
1University of North Carolina at Chapel Hill Chapel Hill North Carolina USA.
Insights
Early enzyme replacement therapy with intrathecal idursulfase-IT may stabilize cognitive development in young children with neuronopathic mucopolysaccharidosis II (MPS II). This treatment shows potential in slowing cognitive decline for these young MPS II patients.
Area of Science:
- Biochemistry
- Genetics
- Pediatrics
Background:
- Neuronopathic mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare genetic disorder affecting cognitive function.
- Previous studies suggested potential benefits of intrathecal idursulfase-IT in older children with MPS II.
Purpose of the Study:
- To investigate the efficacy of intrathecal idursulfase-IT in children with MPS II younger than 3 years.
- To assess the impact of 3-year treatment on cognitive development and cerebrospinal fluid glycosaminoglycans.
Main Methods:
- A 52-week, open-label, single-arm substudy involving nine patients (aged 1.4-3.0 years) with MPS II.
- Cognitive function assessed using Bayley Scales of Infant and Toddler Development (BSID-III) and Differential Ability Scales (DAS-II).
- Cerebrospinal fluid (CSF) total glycosaminoglycans (GAGs) measured to assess treatment effect.
Main Results:
- BSID-III cognitive composite scores remained relatively stable over time, with most patients scoring in the average to low average range.
- Transition to DAS-II resulted in score decreases, but DAS-II General Conceptual Ability scores showed relative stability thereafter.
- CSF GAG concentrations were markedly reduced by week 16 and remained low, indicating treatment efficacy.
Conclusions:
- Intrathecal idursulfase-IT treatment appears to stabilize cognitive development or slow cognitive impairment progression in very young children with neuronopathic MPS II.
- Early intervention with enzyme replacement therapy may be beneficial for cognitive outcomes in this population.
- Further research is warranted to confirm long-term cognitive benefits and optimal treatment timing.
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.
