Comparison of the effects of agalsidase alfa and agalsidase beta on cultured human Fabry fibroblasts and Fabry mice

Hitoshi Sakuraba*, Mai Murata-Ohsawa, Ikuo Kawashima, Youichi Tajima, Masaharu Kotani, Toshio Ohshima, Yasunori Chiba, Minako Takashiba, Yoshifumi Jigami, Tomoko Fukushige, Tamotsu Kanzaki, Kohji Itoh

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)


We compared two recombinant α-Galactosidases developed for enzyme replacement therapy for Fabry disease, agalsidase alfa and agalsidase beta, as to specific α-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 α-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.

Original languageEnglish
Pages (from-to)180-188
Number of pages9
JournalJournal of Human Genetics
Issue number3
Publication statusPublished - 2006 Mar
Externally publishedYes


  • Enzyme replacement therapy
  • Fabry disease
  • Fabry mouse
  • Globotriaosyl ceramide
  • α-Galactosidase

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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