title: Chemical chaperone treatment for galactosialidosis: Effect of NOEV on β-galactosidase activities in fibroblasts.
abstract: BACKGROUND
  Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 β-galactosidase (β-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. Three subtypes are recognized: early infantile, late infantile, and juvenile/adult. There is no specific therapy for patients with galactosialidosis at this time.
  
  
  OBJECTIVE
  The aim of this study was to determine the chaperone effect of N-octyl-4-epi-β-valienamine (NOEV) on β-gal proteins in skin fibroblasts of PPCA-deficit patients.
  
  
  METHODS
  β-Gal and neuraminidase activities were measured for the diagnosis of the patients with galactosialidosis. Western blotting for PPCA protein and direct sequencing for CTSA gene were performed. Cultured skin fibroblast were treated with NOEV.
  
  
  RESULTS
  We report four novel patients with galactosialidosis: one had the early infantile form and the other three had the juvenile/adult form. We found that NOEV stabilized β-gal activity in lysate from cultured skin fibroblasts from these patients. Treatment with NOEV significantly enhanced β-gal activity in cultured skin fibroblasts in the absence of PPCA.
  
  
  CONCLUSIONS
  Our results indicate the possibility that NOEV chaperone therapy might have a beneficial effect, at least in part, for patients with galactosialidosis.
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Mohammad Arif
authors.initials: MA
authors.lastname: Hossain
authors.affiliation: Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Higaki
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Shinpo
authors.affiliation: Division of Functional Genomics, Research Center for Bioscience and Technology, Tottori University, Yonago, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nanba
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ozono
authors.affiliation: Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. Electronic address: norio@ped.med.osaka-u.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Sakai
mesh_terms: D000293:Adolescent; D000328:Adult; D043402:Cathepsin A / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D005347:Fibroblasts / Q000187:drug effects; D016537:Gangliosidosis, GM1 / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D006595:Hexosamines / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D018832:Molecular Chaperones / Q000494:pharmacology; D009154:Mutation; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D006595:Hexosamines; D018832:Molecular Chaperones; C116532:N-octyl-beta-valienamine; C021502:acid beta-galactosidase; D001616:beta-Galactosidase; C468629:CTSA protein, human; D043402:Cathepsin A
keywords: Chaperone; Cherry-red spot; Galactosialidosis; Hydrops fetalis; N-Octyl-4-epi-β-valienamine