| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1999368 | Molecular Genetics and Metabolism | 2008 | 6 Pages |
Fabry disease is a progressive, life-threatening lysosomal storage disorder which is characterized by deficient activity of the lysosomal enzyme α-galactosidase A. Studies have demonstrated that both enzyme preparations currently available for treatment of Fabry disease (i.e., agalsidase beta and agalsidase alfa) elicit immune responses in the majority of patients which negatively influences the reduction of urinary globotriaosylceramide concentration. In the current study, agalsidase beta antibodies were found to be associated with inhibition of α-Gal A enzyme activity in cultured Fabry fibroblast and tissues from Fabry mice. However, the negative effect of antibody formation could be overcome by increasing the dose of enzyme administered to mice. In conclusion, antibody titers and the dose of enzyme influenced α-Gal A enzyme activities in vivo. Further studies are required to investigate to what extend antibody formation impacts on therapeutic responses in antibody positive Fabry patients receiving enzyme replacement therapy and if negative effects can be overcome by adjusting the dose of enzyme.
