alpha-L-iduronidase therapy for mucopolysaccharidosis type I

Area of Science:

• Biochemistry
• Genetics
• Cell Biology

Background:

• Mucopolysaccharidosis type I (MPS I), including Hurler syndrome (MPS IH), is a genetic disorder caused by alpha-L-iduronidase deficiency.
• Over 500 MPS IH patients have undergone hematopoietic cell transplantation (HCT) globally.
• Enzyme replacement therapy (ERT) using recombinant alpha-L-iduronidase (IDUA) is now widely used for less severe MPS I forms.

Purpose of the Study:

• To review the therapeutic delivery applications of alpha-L-iduronidase (IDUA).
• To discuss current and potential future treatment modalities for MPS I.
• To explore the shift towards multimodal therapeutic strategies for MPS I.

Main Methods:

• Review of existing literature on HCT and ERT for MPS I.
• Analysis of the rationale behind current therapeutic approaches.
• Discussion of emerging gene therapy and stem cell strategies.

Main Results:

• HCT has been a long-standing treatment for severe MPS IH.
• ERT effectively treats less severe MPS I, and combination therapy (ERT + HCT) is also utilized.
• The underlying principle for both HCT and ERT is the correction of substrate accumulation via functional IDUA.

Conclusions:

• Current MPS I therapies include HCT and ERT, with combined approaches also in use.
• Future therapeutic strategies may incorporate gene therapy and non-hematopoietic stem cell treatments.
• A transition from unimodal to multimodal therapy for MPS I is anticipated, offering broader treatment options.