Lysosomal enzyme that hydrolyzes terminal α-d-galactose residues in oligosaccharides and galactolipids. Genetic deficiency of the enzyme results in the glycosphingolipid storage disorder known as Fabry's disease. Homodimeric glycoprotein, mol wt ≈101 kDa. Targeted to lysosomes via the mannose-6-phosphate receptor. Identification and role in disease: R. O. Brady et al., N. Engl. J. Med. 276, 1163 (1967). Identification as an α-galactosidase: J. A. Kint, Science 167, 1268 (1970). Use in enzyme replacement therapy: R. J. Desnick et al., Proc. Natl. Acad. Sci. USA 76, 5326 (1979). Review: R. J. Desnick et al. in The Metabolic and Molecular Bases of Inherited Disease, C. R. Scriver et al., Eds. (McGraw-Hill, New York, 7th Ed., 1995) pp 2741-2784.
Human α-galactosidase A produced by recombinant DNA technology in cultured human cells. See: R. F. Selden et al., WO 9811206 (1998 to Transkaryotic Therapies). Clinical pharmacology and pharmacokinetics: R. Schiffmann et al., Proc. Natl. Acad. Sci. USA 97, 365 (2000).
Human α-galactosidase A produced by recombinant DNA technology in Chinese hamster ovary cells. See: R. J. Desnick et al., US 5356804 (1994 to Mt. Sinai School of Med.). Clinical trial in Fabry's disease: C. M. Eng et al., N. Engl. J. Med. 345, 9 (2001).
Enzyme replacement therapy for Fabry's disease.
Enzyme Replacement Therapy