Research in Hurler syndrome (MPS I-H)
This area of hurlersyndrome.org is dedicated to researchers and research-focused clinicians working on Hurler syndrome, the severe form of MPS I. It brings together scientific foundations, translational and preclinical work, clinical research priorities, registry-based evidence and opportunities for collaboration.
Whether your work focuses on lysosomal biology, gene and cell therapy, clinical trials, epidemiology or health services research, this page directs you to MPS I-H specific resources and content.
For researchers and research-focused clinicians only. Content does not replace formal protocols, regulatory guidance or ethics approval.Who this page is for
This section is intended for professionals involved in research across the MPS I-H spectrum, including:
- Basic scientists studying lysosomal function, GAG metabolism and neurodegeneration
- Translational researchers developing gene therapy vectors and systemic delivery platforms
- Clinical researchers in metabolic medicine, transplantation, paediatrics, neurology, cardiology and orthopaedics
- Data scientists and epidemiologists analysing registry and real-world datasets
- Industry partners evaluating MPS I-H as a model indication for emerging platforms
Scientific and clinical questions
Hurler syndrome raises critical questions spanning lysosomal biology, CNS disease, skeletal pathology, transplant medicine and systemic gene delivery. Core research themes include:
- Pathophysiology and mechanisms: Cellular consequences of IDUA deficiency, GAG accumulation, inflammation and fibrosis affecting CNS and bone.
- Natural history and residual morbidity: Long-term outcomes following HSCT and ERT, including persistent skeletal, cardiac and neurocognitive disease.
- Unmet need and quality of life: Procedural burden, pain, disability, psychosocial impact and family outcomes.
Gene therapy and advanced therapeutic approaches
MPS I-H is a strong candidate for systemic gene therapy due to its well-defined biochemical defect, severe untreated course and established HSCT and ERT standards that provide a clear clinical baseline.
Rationale for gene therapy
- Limits of HSCT and ERT in CNS and skeletal disease
- Need for durable, body-wide enzyme delivery
Vector design and mechanism
- Lentiviral construct and promoter selection
- IDUA transgene and tissue targeting strategy
Preclinical programme
- Animal models, dosing and endpoints
- Biochemical, histological and behavioural outcomes
Animal models, biomarkers and experimental design
Models and study design
- Established mouse models of MPS I-H
- Dosing strategies and control groups
Efficacy endpoints
- IDUA activity and GAG reduction
- CNS, skeletal and functional outcomes
Safety and biodistribution
- Off-target effects and insertion concerns
- Tissue distribution and immune responses
Observational and interventional clinical research
Clinical research in MPS I-H addresses early diagnosis, optimisation of standard care, long-term outcomes and assessment of new therapies.
- Comparative outcomes after HSCT with or without ERT
- Long-term somatic and neurocognitive trajectories
- Longitudinal registries and structured follow-up cohorts
- Translational pathways from preclinical studies to first-in-human trials
Clinical trials landscape
The MPS I-H trial landscape is evolving, spanning disease-modifying therapies, supportive interventions and quality-of-life research.
- Overview of trial types and therapeutic targets
- Context relative to HSCT and ERT standards
- Guidance on accessing information via formal registries
Publications and key papers
The Publications section provides a curated entry point for deeper literature review across basic, translational and clinical research.
View all publicationsConducting research responsibly
- Align ethics and regulatory approvals with study design
- Use age-appropriate consent and assent processes
- Partner with patient organisations to co-develop materials
- Be transparent about data governance and sharing
Opportunities to collaborate
Progress in MPS I-H research relies on collaboration across academia, clinical networks, patient groups and industry.
- Joint basic and translational research projects
- Shared registry analyses and outcomes research
- Multi-centre clinical studies and trials
Key messages for researchers
- MPS I-H is a powerful model for lysosomal disease and systemic gene delivery research
- The Research Hub centralises science, translational work and clinical outcomes
- Registries and long-term follow-up are essential to define real-world impact
- Ethical, patient-centred collaboration is critical for future progress