Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice.
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.
Sakuraba
Hitoshi
H
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.
Murata-Ohsawa
Mai
M
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.
Kawashima
Ikuo
I
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.
Tajima
Youichi
Y
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.
Kotani
Masaharu
M
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.
Ohshima
Toshio
T
Laboratory for Developmental Neurology, Brain Science Institute, RIKEN, Wako, Japan.
Chiba
Yasunori
Y
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Takashiba
Minako
M
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Jigami
Yoshifumi
Y
Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, Tsukuba, Japan.
Fukushige
Tomoko
T
Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Kanzaki
Tamotsu
T
Department of Dermatology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Itoh
Kohji
K
Department of Medicinal Biotechnology, Institute for Medicinal Resources, Graduate School of Pharmaceutical Sciences, The University of Tokushima, Tokushima, Japan.
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*
D007527:Isoenzymes; D011994:Recombinant Proteins; C000627036:agalsidase alfa; D000519:alpha-Galactosidase; C459420:agalsidase beta