Immune Tolerance Induction in Hurler Syndrome (ITIMHS)


Mucopolysacchirdosis Type IH (Hurler Syndrome)

Full Study Name

A Single Centre Study Investigating the Safety and Efficacy of an Immune Modulation Regimen in Mitigating the Alloimmune Response to Intravenous Laronidase in Infants With Severe Mucopolysaccharidosis type I (Hurler syndrome) Prior to Haematopoietic Stem Cell Transplantation

Study ID



Manchester University NHS Foundation Trust

Local Principal Investigator

Simon Jones

Study Status


Main Aims

The objective of this trial is to investigate the safety and efficacy of methotrexate as an immune tolerance induction agent in mitigating the alloimmune response to enzyme replacement therapy with laronidase in severe MPS I.

Inclusion Criteria
  • A diagnosis of MPS I as defined by deficient α-L-iduronidase activity in leukocytes or cultured fibroblasts, in a laboratory accepted by the investigators
    • Clinical status consistent with severe Hurler phenotype
    • OR If available, mutations consistent with a classical Hurler genotype e.g. homozygosity or compound heterozygosity for nonsense mutations (Q70X, W402X) in IDUA gene
  • Age ≥3 months and ≤2.5 years at diagnosis
  • Decision to offer HSCT with an appropriate donor after a short period (minimum 4 weeks) of ERT
Exclusion Criteria
  • The patient has previously received intravenous laronidase
  • The patient has undergone haematopoietic stem cell transplantation
  • The patient has a known primary immune defect
  • The patient has a known sensitivity or allergy to methotrexate
  • The patient has known contraindications to receiving methotrexate such as pre-existing hepatic or renal dysfunction
  • The patient has received any immunomodulatory or immunosuppressive medication within 90 days prior to enrolment
  • The patient has been exposed to any other investigational product within 90 days prior to enrolment in the trial
  • The patient has any clinically significant organic disease (with the exception of symptoms relating to MPS I), including cardiovascular, hepatic, pulmonary, neurologic or renal disease, other serious intercurrent illness or extenuating circumstances, that, in the opinion of the investigator would preclude participation in the trial or potentially decrease survival
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