Skip Navigation


Glycobiology Advance Access originally published online on January 3, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
13/4/305    most recent
cwg034v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (41)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Lee, K.
Right arrow Articles by Edmunds, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lee, K.
Right arrow Articles by Edmunds, T.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Glycobiology, 2003, Vol. 13, No. 4 305-313
© 2003 Oxford University Press

A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease

Karen Lee, Xiaoying Jin, Kate Zhang, Lorraine Copertino, Laura Andrews, Jennifer Baker-Malcolm, Laura Geagan, Huawei Qiu, Keirsten Seiger, Debra Barngrover, John M. McPherson and Tim Edmunds1

Cell and Protein Therapeutics, Genzyme Corporation, P.O. Box 9322, Framingham, MA 01701-9322, USA

Received on October 8, 2002; revised on November 19, 2002; accepted on November 22, 2002

Fabry disease is a lysosomal storage disease arising from deficiency of the enzyme {alpha}-galactosidase A. Two recombinant protein therapeutics, Fabrazyme (agalsidase beta) and Replagal (agalsidase alfa), have been approved in Europe as enzyme replacement therapies for Fabry disease. Both contain the same human enzyme, {alpha}-galactosidase A, but they are produced using different protein expression systems and have been approved for administration at different doses. To determine if there is recognizable biochemical basis for the different doses, we performed a comparison of the two drugs, focusing on factors that are likely to influence biological activity and availability. The two drugs have similar glycosylation, both in the type and location of the oligosaccharide structures present. Differences in glycosylation were mainly limited to the levels of sialic acid and mannose-6-phosphate present, with Fabrazyme having a higher percentage of fully sialylated oligosaccharides and a higher level of phosphorylation. The higher levels of phosphorylated oligomannose residues correlated with increased binding to mannose-6-phosphate receptors and uptake into Fabry fibroblasts in vitro. Biodistribution studies in a mouse model of Fabry disease showed similar organ uptake. Likewise, antigenicity studies using antisera from Fabry patients demonstrated that both drugs were indistinguishable in terms of antibody cross-reactivity. Based on these studies and present knowledge regarding the influence of glycosylation on protein biodistribution and cellular uptake, the two protein preparations appear to be functionally indistinguishable. Therefore, the data from these studies provide no rationale for the use of these proteins at different therapeutic doses.

1 To whom correspondence should be addressed; e-mail: tim.edmunds{at}genzyme.com


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
A. I. Guce, N. E. Clark, E. N. Salgado, D. R. Ivanen, A. A. Kulminskaya, H. Brumer III, and S. C. Garman
Catalytic Mechanism of Human {alpha}-Galactosidase
J. Biol. Chem., February 5, 2010; 285(6): 3625 - 3632.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
M. Ries, J. T. Clarke, C. Whybra, A. Mehta, K. S. Loveday, R. O. Brady, M. Beck, and R. Schiffmann
Enzyme Replacement in Fabry Disease: Pharmacokinetics and Pharmacodynamics of Agalsidase Alfa in Children and Adolescents
J. Clin. Pharmacol., October 1, 2007; 47(10): 1222 - 1230.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
G. M. Pastores, E. Boyd, K. Crandall, A. Whelan, L. Piersall, and N. Barnett
Safety and pharmacokinetics of agalsidase alfa in patients with Fabry disease and end-stage renal disease
Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1920 - 1925.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
D. G. Warnock
Enzyme Replacement Therapy and Fabry Kidney Disease: Quo Vadis?
J. Am. Soc. Nephrol., May 1, 2007; 18(5): 1368 - 1370.
[Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
J. T.R. Clarke
Narrative Review: Fabry Disease
Ann Intern Med, March 20, 2007; 146(6): 425 - 433.
[Abstract] [Full Text] [PDF]

Home page
 J. Am. Soc. Nephrol.Home page
E. I. Christensen, Q. Zhou, S. S. Sorensen, A. K. Rasmussen, C. Jacobsen, U. Feldt-Rasmussen, and R. Nielsen
Distribution of {alpha}-Galactosidase A in Normal Human Kidney and Renal Accumulation and Distribution of Recombinant {alpha}-Galactosidase A in Fabry Mice
J. Am. Soc. Nephrol., March 1, 2007; 18(3): 698 - 706.
[Abstract] [Full Text] [PDF]

Home page
 GlycobiologyHome page
V. I. Otto, E. Damoc, L. N. Cueni, T. Schurpf, R. Frei, S. Ali, N. Callewaert, A. Moise, J. A. Leary, G. Folkers, et al.
N-Glycan structures and N-glycosylation sites of mouse soluble intercellular adhesion molecule-1 revealed by MALDI-TOF and FTICR mass spectrometry
Glycobiology, November 1, 2006; 16(11): 1033 - 1044.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. H. LeBowitz, J. H. Grubb, J. A. Maga, D. H. Schmiel, C. Vogler, and W. S. Sly
Glycosylation-independent targeting enhances enzyme delivery to lysosomes and decreases storage in mucopolysaccharidosis type VII mice
PNAS, March 2, 2004; 101(9): 3083 - 3088.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.