A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome)

Mol Genet Metab. 2007 Mar;90(3):329-37. doi: 10.1016/j.ymgme.2006.09.001. Epub 2006 Dec 20.


Objective: To evaluate the safety and explore the efficacy of idursulfase (recombinant human iduronate-2-sulfatase) treatment for mucopolysaccharidosis II (MPS II).

Study design: Twelve patients were enrolled into a randomized, double-blind, placebo-controlled trial for 24 weeks followed by an open-label extension study. Three groups of 4 patients were enrolled sequentially, with 3 patients in each group receiving idursulfase and 1 patient receiving placebo. The first group received idursulfase at 0.15 mg/kg infused every other week with the 2nd and 3rd groups receiving 0.5 and 1.5 mg/kg, respectively. After 24 weeks the placebo-treated patients were changed to idursulfase at the dose of their group. The primary endpoint was a change from baseline in urinary excretion of glycosaminoglycans. Results were pooled for analysis by ANOVA and compared to baseline.

Results: Urinary glycosaminoglycans were reduced within 2 weeks of initiating idursulfase and were decreased 49% after 48 weeks of treatment (P<0.0001). Both liver and spleen volume were decreased at 24 weeks (P<0.01) and 48 weeks (P<0.001). The 6-minute walk test distance increased an average of 48 meters after 48 weeks (P=0.013). Six patients in the higher dose groups developed IgG antibodies that did not influence the clinical effects of idursulfase.

Conclusions: This study describes the first experience with enzyme replacement therapy for the treatment of patients with MPS II. Idursulfase was generally well tolerated and was associated with reductions in urine glycosaminoglycans levels and organ size, as well as an increased 6-minute walk test distance.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Double-Blind Method
  • Glycosaminoglycans / urine
  • Humans
  • Iduronate Sulfatase / administration & dosage
  • Iduronate Sulfatase / adverse effects
  • Iduronate Sulfatase / immunology
  • Iduronate Sulfatase / therapeutic use*
  • Immunoglobulin G / biosynthesis
  • Infusions, Intravenous
  • Joints / drug effects
  • Joints / physiopathology
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Mucopolysaccharidosis II / drug therapy*
  • Mucopolysaccharidosis II / pathology
  • Mucopolysaccharidosis II / physiopathology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / immunology
  • Recombinant Proteins / therapeutic use
  • Respiratory Function Tests
  • Safety
  • Spleen / drug effects
  • Spleen / pathology


  • Glycosaminoglycans
  • Immunoglobulin G
  • Recombinant Proteins
  • Iduronate Sulfatase