ENOrphanet Journal of Rare Diseases | Impact of Bone Marrow Transplantation on Neurodevelopmental Trajectories in Mucopolysaccharidosis: A Subtype-Specific and Age-Dependent Efficacy Study
Date: April 05, 2025
Classification: Frontiers
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This study systematically evaluated the impact of hematopoietic stem cell transplantation (HSCT) on neurodevelopmental trajectories in patients with mucopolysaccharidosis (MPS), revealing significant modulatory effects of disease subtype and transplantation age on outcomes. The study emphasizes the optimizing effects of early transplantation on motor and language functions, and demonstrates the utility of GDS-C in longitudinal monitoring.
Literature Overview
This paper, titled Allogeneic hematopoietic stem cell transplantation modulates neurodevelopmental trajectories in mucopolysaccharidosis: a longitudinal study of subtype-specific outcomes and age-dependent efficacy, was published in the Orphanet Journal of Rare Diseases. It reviews and summarizes the neurodevelopmental changes in 57 Chinese children with mucopolysaccharidosis (MPS) before and after hematopoietic stem cell transplantation (HSCT). The study employed a modified version of the Griffiths Developmental Scale (GDS-C) to conduct multi-timepoint assessments, revealing subtype- and age-dependent differences in transplant efficacy. It further notes that HSCT yields the most significant motor improvement in MPS type III patients, while older transplantation age correlates with reduced efficacy. The findings provide critical evidence for personalized treatment and optimizing transplant timing in MPS patients.
Background
Mucopolysaccharidosis (MPS) is a group of rare genetic disorders caused by lysosomal enzyme deficiencies that lead to the accumulation of glycosaminoglycans (GAGs). These disorders, including multiple subtypes (e.g., types I, II, and III), are often accompanied by progressive neurodevelopmental deterioration, such as cognitive impairment, language delay, behavioral abnormalities, and motor dysfunction. Hematopoietic stem cell transplantation (HSCT) is a potential therapeutic approach that can supply donor-derived enzyme replacement, thus improving disease progression. However, its efficacy varies significantly across subtypes and age groups. For instance, patients with MPS type II have reduced blood-brain barrier permeability, limiting transplant efficacy, whereas MPS type I patients show better outcomes due to higher GAG clearance efficiency associated with α-L-iduronidase deficiency. Additionally, previous studies suggest that early intervention plays a crucial role in neuroprotection, yet there has been a lack of systematic assessment tools tailored for Chinese populations. GDS-C, a culturally adapted developmental scale covering motor, language, coordination, visual, and practical reasoning domains, addresses the limitations of traditional tools in non-Western populations. This study, through longitudinal evaluation of neurodevelopmental trajectories before and after transplantation, quantitatively demonstrated subtype-specific and age-dependent efficacy differences for the first time, offering key evidence for clinical decision-making.
Study Methods and Experiments
The study enrolled 57 Chinese children with mucopolysaccharidosis (MPS) aged 1 to 8 years. All participants underwent allogeneic hematopoietic stem cell transplantation (HSCT) between 2019 and 2024 and were assessed using the GDS-C at pre-transplantation, 3 months post-transplantation, 12 months post-transplantation, and 24 months post-transplantation. A prospective cohort design was used, with linear mixed-effects regression (LMER) models applied to evaluate the impact of timepoints, transplantation age, sex, and disease subtype on neurodevelopmental trajectories. Exclusion criteria included comorbid severe brain injury, epilepsy, sensory impairments, chromosomal abnormalities, other metabolic diseases, and prior enzyme replacement therapy (ERT), ensuring independent evaluation of transplant efficacy.
Key Findings and Conclusions
Significance and Future Directions
This study represents the first systematic assessment of HSCT's impact on neurodevelopmental trajectories in Chinese MPS patients, identifying disease subtype and transplantation age as key moderators of treatment efficacy. It provides evidence for optimal transplant timing in MPS type III patients and recommends integrating neurodevelopmental training to delay functional decline. Future studies should include larger cohorts of MPS type III patients, quantify changes in cerebrospinal fluid GAG levels, and explore synergistic effects of HSCT combined with ERT or other adjuvant therapies. Additionally, dynamic prediction models based on GDS-C should be developed to support clinical decision-making for individualized transplant and rehabilitation strategies.
Conclusion
This study evaluated neurodevelopmental changes in 57 Chinese MPS patients pre- and post-bone marrow transplantation using GDS-C, revealing heterogeneity in HSCT efficacy across subtypes and ages. Findings indicate that MPS type III patients experience the most significant improvement in motor function following transplantation, whereas MPS type II patients show limited language improvement. Earlier transplantation age correlates with better outcomes, underscoring the importance of early intervention. Despite short-term neurodevelopmental gains post-transplantation, functional decline across all domains was observed at 24 months, suggesting that HSCT alone is insufficient to fully reverse neurodegeneration and must be supported by rehabilitation. The study provides critical evidence for optimizing transplant timing and developing subtype-specific rehabilitation strategies, while confirming the applicability of GDS-C in the Chinese population. Future studies should expand to multi-center designs, integrate imaging data, and explore combination therapies to enhance long-term outcomes.
