Evaluation of early treatment with intravenous idursulfase and intrathecal idursulfase‐ <scp>IT</scp> on cognitive function in siblings with neuronopathic mucopolysaccharidosis <scp>II</scp>
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".