Transplant outcomes in mucopolysaccharidoses

Area of Science:

• Biochemistry
• Genetics
• Pediatrics

Background:

• Mucopolysaccharidoses (MPSs) are inherited metabolic disorders (IMDs) caused by genetic defects leading to glycosaminoglycan (GAG) accumulation.
• MPSs affect multiple organ systems, including the central nervous, musculoskeletal, and cardiorespiratory systems.
• Hurler syndrome (MPS IH) is the most severe form and serves as a model for MPS research.

Purpose of the Study:

• To review the clinical experiences and current status of allogeneic hematopoietic stem cell transplantation (HSCT) for MPS.
• To compare umbilical cord blood transplant (UCBT) with traditional bone marrow transplantation for MPS.
• To provide updated therapy guidelines for MPS patients.

Main Methods:

• Review of published clinical experiences and institutional data on HSCT for MPS.
• Analysis of outcomes in patients treated with unrelated donor (URD) UCBT versus bone marrow grafts.
• Discussion of the mechanism of action for HSCT in delivering enzyme therapy to the brain.

Main Results:

• HSCT improves somatic organ function, neurocognitive outcomes, quality of life, and survival in MPS patients, especially when performed early.
• Enzyme replacement therapy (ERT) is limited by its inability to cross the blood-brain barrier.
• URD-UCBT has shown favorable outcomes and increased accessibility compared to historical bone marrow grafts.

Conclusions:

• HSCT is a superior therapeutic option for MPS compared to ERT due to its ability to provide permanent enzyme replacement, including in the central nervous system.
• URD-UCBT represents a significant advancement, improving access to life-altering HSCT for MPS patients.
• Early intervention with HSCT is crucial for maximizing therapeutic benefits and long-term survival in MPS.