title: Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations.
abstract: BACKGROUND
  Following a Phase III, randomized, double-blind, placebo (PBO)-controlled, multinational study in subjects with mucopolysaccharidosis IVA (MPS IVA), enzyme replacement therapy (ERT) of elosulfase alfa has been approved in several countries. The study was designed to evaluate safety and efficacy of elosulfase alfa in patients with MPS IVA aged 5 years and older.
  
  
  METHODS
  Outcomes of clinical trials for MPS IVA have been described. Subjects received either 2.0 mg/kg/week, 2.0 mg/kg/every other week, or PBO, for 24 weeks. The primary endpoint was the change from baseline 6-min walk test (6MWT) distance compared to PBO. The 6MWT results improved in patients receiving 2 mg/kg weekly compared to PBO. The every other week regimen resulted in walk distances comparable to PBO. There was no change from baseline in the 3 Min Stair Climb Test in both treatment groups. Following completion of the initial study, patients, who continued to receive elosulfase alfa 2 mg/kg weekly (QW) for another 48 weeks (for a total of up to 72-week exposure), did not show additional improvement on 6MWT.
  
  
  CONCLUSIONS
  We suggest that ERT is a therapeutic option for MPS IVA, providing a modest effect and the majority of the effects are seen in the soft tissues.
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA; Department of Pediatrics, Gifu University, Gifu, Japan, Japan.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sawamoto
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA; Department of Medical Informatics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bober
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA; Department of Biological Sciences, University of Delaware, Newark, DE, USA.
authors.forename: Francyne
authors.initials: F
authors.lastname: Kubaski
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA; Department of Medical Informatics, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yasuda
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA.
authors.forename: Shaukat
authors.initials: S
authors.lastname: Khan
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Alméciga-Díaz
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, School of Sciences, Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Rd., Wilmington, DE 19899-0269, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Mackenzie
authors.affiliation: Department of Pediatrics, Gifu University, Gifu, Japan, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
keywords: Chondroitin-6-sulfate; enzyme replacement therapy; keratan sulfate; mucopolysaccharidosis IVA; skeletal dysplasia