title: Therapies of mucopolysaccharidosis IVA (Morquio A syndrome).
abstract: BACKGROUND
  Morquio A syndrome (mucopolysaccharidosis type IVA, MPS IVA) is one of the lysosomal storage diseases and is caused by the deficiency ofN-acetylgalactosamine-6-sulfate sulfatase (GALNS). Deficiency of this enzyme leads to accumulation of glycosaminoglycans (GAGs), keratan sulfate (KS) and chondroitin-6-sulfate (C6S). The majority of KS is produced by chondrocytes, and therefore, the undegraded substrates accumulate mainly in cells and extracelluar matrix (ECM) of cartilage. This has a direct impact on cartilage and bone development, leading to systemic skeletal dysplasia. In patients with Morquio A, cartilage cells are vacuolated, and this results in abnormal chondrogenesis and/or endochondral ossification.
  
  
  METHODS
  This article describes the advanced therapies of Morquio A, focused on enzyme replacement therapy (ERT) and gene therapy to deliver the drug to avascular bone lesions. ERT and gene therapies for other types of MPS are also discussed, which provide therapeutic efficacy to bone lesions.
  
  
  CONCLUSIONS
  ERT, gene therapy and hematopietic stem therapy are clinically and/or experimentally conducted. However, there is no effective curative therapy for bone lesion to date. One of the limitations for Morquio A therapy is that targeting avascular cartilage tissues remains an unmet challenge. ERT or gene therapy with bone-targeting system will improve the bone pathology and skeletal manifestations more efficiently.
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA ; Nemours/Alfred I. duPont Hospital for Children, Skeletal Dysplasia Center, Nemours Biomedical Research, 1600 Rockland Rd., Wilmington, DE 19803, USA.
authors.forename: Shunji
authors.initials: S
authors.lastname: Tomatsu
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Alméciga-Díaz
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Hector
authors.initials: H
authors.lastname: Barbosa
authors.affiliation: Saint Louis University, Department of Pediatrics, St. Louis, MO, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Montaño
authors.affiliation: Institute for the Study of Inborn Errors of Metabolism, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Barrera
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Eriko
authors.initials: E
authors.lastname: Yasuda
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Mackenzie
authors.affiliation: Professor and Director, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mason
authors.affiliation: Gifu University, Medical Education Development Center, Gifu, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Gifu University, Department of Pediatrics, Gifu, Japan.
authors.forename: Kenji E
authors.initials: KE
authors.lastname: Orii
authors.affiliation: Gifu University, Department of Pediatrics, Gifu, Japan.
authors.forename: Tadao
authors.initials: T
authors.lastname: Orii
keywords: GALNS; enzyme replacement therapy; gene therapy; keratan sulfate; mucopolysaccharidosis IVA; tandem mass spectrometry