Developmental outcome in five children with Hurler syndrome after stem cell transplantation: a pilot study

Area of Science:

• Lysosomal storage diseases
• Neurodegenerative disorders
• Hematopoietic stem cell transplantation

Background:

• Hurler syndrome (MPS1H) is a fatal neurodegenerative lysosomal storage disease due to alpha-L-iduronidase deficiency.
• Enzyme replacement therapy is limited to non-central nervous system organs.
• Hematopoietic stem cell transplantation (SCT) is the only treatment to prevent neurodegeneration, but traditional protocols have high toxicity and graft failure rates.

Purpose of the Study:

• To evaluate the developmental outcomes of Hurler syndrome patients treated with a novel, well-tolerated, fludarabine-based, radiation-free conditioning regimen for SCT.
• To assess the efficacy of this new SCT strategy in preventing neurodegeneration and improving clinical manifestations.

Main Methods:

• Five patients with Hurler syndrome (MPS1H) received SCT using a fludarabine-based, radiation-free conditioning regimen.
• Developmental outcomes were assessed using the Denver Developmental Screening Test before and annually after SCT.
• Intracranial lesions and head circumference were monitored post-transplantation.

Main Results:

• All five patients achieved engraftment and are ambulatory.
• No neurodegeneration was observed; all patients demonstrated psychomotor development without decline.
• Regression of intracranial lesions and a relative reduction in head circumference were observed in all patients post-SCT.

Conclusions:

• A fludarabine-based, radiation-free conditioning regimen for SCT is a safe and effective strategy for treating Hurler syndrome (MPS1H).
• This approach successfully prevents neurodegeneration, promotes psychomotor development, and leads to regression of intracranial lesions.
• This novel SCT protocol offers a promising alternative to traditional transplantation methods for Hurler syndrome patients.