Comparative therapeutic effects of velaglucerase alfa and imiglucerase in a Gaucher disease mouse model

Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic propertie...

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Bibliographic Details
Published in:PloS one 2010-05, Vol.5 (5), p.e10750
Main Authors: Xu, You-Hai, Sun, Ying, Barnes, Sonya, Grabowski, Gregory A
Format: Article
Language:English
Subjects:
Amino acids
Analysis
Animals
Antibody Formation - drug effects
Biochemistry
Bone marrow
Catalytic Domain
Children & youth
Clinical outcomes
Cryptococcus neoformans
Disease
Disease Models, Animal
Drug delivery systems
Enzyme Inhibitors - pharmacology
Enzyme Stability - drug effects
Enzymes
Fibroblasts
Fibrosarcoma
Gaucher Disease - drug therapy
Gaucher's disease
Genetics and Genomics/Disease Models
Genetics and Genomics/Genetics of Disease
Glucosidase
Glucosylceramidase - antagonists & inhibitors
Glucosylceramidase - pharmacokinetics
Glucosylceramidase - pharmacology
Glucosylceramidase - therapeutic use
Guanylate cyclase
Health aspects
Hepatocytes
Humans
Hydrogen-Ion Concentration - drug effects
Hypersensitivity
Immunoglobulin E
Immunoglobulin G
Inhibitory Concentration 50
Injections, Intravenous
Interstitial cells
Liver
Lungs
Mice
Mutation
Organ Specificity - drug effects
Pediatrics
Peptide Hydrolases - metabolism
Pharmacodynamics
Pharmacokinetics
Pharmacology
Reversing
Saposins - metabolism
Sarcoma
Spleen
Storage
Therapeutic applications
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Summary:Gaucher disease type 1 is caused by the defective activity of the lysosomal enzyme, acid beta-glucosidase (GCase). Regular infusions of purified recombinant GCase are the standard of care for reversing hematologic, hepatic, splenic, and bony manifestations. Here, similar in vitro enzymatic properties, and in vivo pharmacokinetics and pharmacodynamics (PK/PD) and therapeutic efficacy of GCase were found with two human GCases, recombinant GCase (CHO cell, imiglucerase, Imig) and gene-activated GCase (human fibrosarcoma cells, velaglucerase alfa, Vela), in a Gaucher mouse, D409V/null. About 80+% of either enzyme localized to the liver interstitial cells and
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0010750