A phase I/II clinical trial of enzyme replacement therapy in mucopolysaccharidosis II (Hunter syndrome).
OBJECTIVE
To evaluate the safety and explore the efficacy of idursulfase (recombinant human iduronate-2-sulfatase) treatment for mucopolysaccharidosis II (MPS II).


METHODS
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.
Muenzer
Joseph
J
University of North Carolina, Department of Pediatrics, CB # 7487, Chapel Hill, NC 27599-7487, USA. muenzer@med.unc.edu <muenzer@med.unc.edu>
Gucsavas-Calikoglu
Muge
M
McCandless
Shawn E
SE
Schuetz
Thomas J
TJ
Kimura
Alan
A
D000293:Adolescent; D000328:Adult; D002648:Child; D004311:Double-Blind Method; D006025:Glycosaminoglycans / Q000652:urine; D006801:Humans; D007066:Iduronate Sulfatase / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007262:Infusions, Intravenous; D007596:Joints / Q000187:drug effects / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D016532:Mucopolysaccharidosis II / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D012129:Respiratory Function Tests; D012449:Safety; D013154:Spleen / Q000187:drug effects / Q000473:pathology
D006025:Glycosaminoglycans; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D007066:Iduronate Sulfatase