title: Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice.
abstract: We compared two recombinant alpha-galactosidases developed for enzyme replacement therapy for Fabry disease, agalsidase alfa and agalsidase beta, as to specific alpha-galactosidase activity, stability in plasma, mannose 6-phosphate (M6P) residue content, and effects on cultured human Fabry fibroblasts and Fabry mice. The specific enzyme activities of agalsidase alfa and agalsidase beta were 1.70 and 3.24 mmol h(-1) mg protein(-1), respectively, and there was no difference in stability in plasma between them. The M6P content of agalsidase beta (3.6 mol/mol protein) was higher than that of agalsidase alfa (1.3 mol/mol protein). The administration of both enzymes resulted in marked increases in alpha-galactosidase activity in cultured human Fabry fibroblasts, and Fabry mouse kidneys, heart, spleen and liver. However, the increase in enzyme activity in cultured fibroblasts, kidneys, heart and spleen was higher when agalsidase beta was used. An immunocytochemical analysis revealed that the incorporated recombinant enzyme degraded the globotriaosyl ceramide accumulated in cultured Fabry fibroblasts in a dose-dependent manner, with the effect being maintained for at least 7 days. Repeated administration of agalsidase beta apparently decreased the number of accumulated lamellar inclusion bodies in renal tubular cells of Fabry mice.
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan. sakuraba@rinshoken.or.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sakuraba
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.|CREST, JST, Kawaguchi, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Murata-Ohsawa
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kawashima
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Tajima
authors.affiliation: Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Tokyo Metropolitan Organization for Medical Research, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo, 113-8613, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kotani
authors.affiliation: Laboratory for Developmental Neurology, Brain Science Institute, RIKEN, Wako, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.affiliation: Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Takashiba
authors.affiliation: Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Jigami
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Fukushige
authors.affiliation: Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kanzaki
authors.affiliation: Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Kohji
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D000795:Fabry Disease / Q000188:drug therapy* / Q000473:pathology; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D007527:Isoenzymes / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D011994:Recombinant Proteins; D000519:alpha-Galactosidase / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta