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Reduced alpha-Gal A enzyme activity in Fabry fibroblast cells and Fabry mice tissues induced by serum from antibody positive patients with Fabry disease.
- Source :
-
Molecular genetics and metabolism [Mol Genet Metab] 2008 Jul; Vol. 94 (3), pp. 313-8. Date of Electronic Publication: 2008 May 05. - Publication Year :
- 2008
-
Abstract
- Fabry disease is a progressive, life-threatening lysosomal storage disorder which is characterized by deficient activity of the lysosomal enzyme alpha-galactosidase A. Studies have demonstrated that both enzyme preparations currently available for treatment of Fabry disease (i.e., agalsidase beta and agalsidase alpha) 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 alpha-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 alpha-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.
- Subjects :
- Adolescent
Adult
Animals
Antibodies blood
Cells, Cultured
Child
Disease Models, Animal
Fabry Disease immunology
Fabry Disease pathology
Fibroblasts metabolism
Fibroblasts pathology
Humans
Kidney enzymology
Liver enzymology
Lung enzymology
Male
Mice
Mice, Knockout
Middle Aged
Myocardium enzymology
Spleen enzymology
alpha-Galactosidase antagonists & inhibitors
alpha-Galactosidase genetics
alpha-Galactosidase immunology
Antibodies pharmacology
Fabry Disease chemically induced
Fabry Disease enzymology
Fibroblasts enzymology
Serum immunology
alpha-Galactosidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1096-7206
- Volume :
- 94
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular genetics and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 18456533
- Full Text :
- https://doi.org/10.1016/j.ymgme.2008.03.008