title: Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase).
abstract: OBJECTIVE
  To confirm the efficacy and safety of recombinant human alpha-L-iduronidase (laronidase) in patients with mucopolysaccharidosis I (MPS I).
  
  
  METHODS
  This was a randomized, double-blinded, multinational study of 45 patients with MPS I administered 100 U/kg (0.58 mg/kg) laronidase, or placebo intravenously weekly for 26 weeks. The coprimary efficacy end points compared the median change from baseline to week 26 between groups in percentage of predicted normal forced vital capacity (FVC) and in 6-minute walk test (6MWT) distance through the use of the Wilcoxon rank sum test.
  
  
  RESULTS
  The laronidase (n=22) and placebo (n=23) groups had similar baseline characteristics. After 26 weeks, patients receiving laronidase compared with placebo showed mean improvements of 5.6 percentage points in percent of predicted normal FVC (median, 3.0; P=.009) and 38.1 meters in 6MWT distance (median, 38.5; P=.066; P=.039, analysis of covariance). Laronidase also significantly reduced hepatomegaly and urinary glycosaminoglycans, and, in more severely affected patients, improved sleep apnea/hypopnea and shoulder flexion. Laronidase was well-tolerated. Nearly all patients receiving enzyme had development of IgG antibodies, without apparent clinical effects.
  
  
  CONCLUSIONS
  In patients with MPS I, laronidase significantly improves respiratory function and physical capacity, reduces glycosaminoglycan storage, and has a favorable safety profile.
authors.affiliation: Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital, Manchester, United Kingdom. ed.wraith@cmmc.nhs.uk
authors.forename: James E
authors.initials: JE
authors.lastname: Wraith
authors.forename: Lorne A
authors.initials: LA
authors.lastname: Clarke
authors.forename: Michael
authors.initials: M
authors.lastname: Beck
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Kolodny
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Pastores
authors.forename: Joseph
authors.initials: J
authors.lastname: Muenzer
authors.forename: David M
authors.initials: DM
authors.lastname: Rapoport
authors.forename: Kenneth I
authors.initials: KI
authors.lastname: Berger
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Swiedler
authors.forename: Emil D
authors.initials: ED
authors.lastname: Kakkis
authors.forename: Tanja
authors.initials: T
authors.lastname: Braakman
authors.forename: Elenie
authors.initials: E
authors.lastname: Chadbourne
authors.forename: Karen
authors.initials: K
authors.lastname: Walton-Bowen
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Cox
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007068:Iduronidase / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008059:Mucopolysaccharidosis I / Q000150:complications / Q000188:drug therapy*; D011994:Recombinant Proteins; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology; D018709:Statistics, Nonparametric
chemical_list: D011994:Recombinant Proteins; D007068:Iduronidase