Characterization of a chemically modified plant cell culture expressed human α-Galactosidase-A enzyme for treatment of Fabry disease
| Autor: | Avidor Shulman, Tali Kizhner, Yaniv Azulay, David Aviezer, Gil Arvatz, Mariana Hainrichson, Ilya Ruderfer, Yoram Tekoah, Yoseph Shaaltiel |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Glycosylation Endocrinology Diabetes and Metabolism Globotriaosylceramide Mannose Mannose 6-phosphate Kidney Biochemistry Fucose Mice chemistry.chemical_compound Endocrinology Enzyme Stability Tobacco Genetics medicine Animals Enzyme Replacement Therapy Molecular Biology Cells Cultured Skin chemistry.chemical_classification Heart medicine.disease Fabry disease Recombinant Proteins Isoenzymes Enzyme Liver chemistry Cell culture alpha-Galactosidase Fabry Disease Spleen |
| Zdroj: | Molecular Genetics and Metabolism. 114:259-267 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2014.08.002 |
| Popis: | Fabry disease is an X-linked recessive disorder caused by the loss of function of the lysosomal enzyme α-Galactosidase-A. Although two enzyme replacement therapies (ERTs) are commercially available, they may not effectively reverse some of the Fabry pathology. PRX-102 is a novel enzyme for the therapy of Fabry disease expressed in a BY2 Tobacco cell culture. PRX-102 is chemically modified, resulting in a cross-linked homo-dimer. We have characterized the in-vitro and in-vivo properties of PRX-102 and compared the results with the two commercially produced α-Galactosidase-A enzymes. Results show that PRX-102 has prolonged in-vitro stability in plasma, after 1h incubation it retains 30% activity compared with complete inactivation of the commercial enzymes. Under lysosomal-like conditions PRX-102 maintains over 80% activity following 10 days of incubation, while commercial enzymes become inactive after 2days. Pharmacokinetic profile of PRX-102 measured in male Fabry mice shows a 10 fold increase in t1/2 in mice (581min) compared to approved drugs. The enzyme has significantly different kinetic parameters to the alternative ERTs available (p-value |
| Databáze: | OpenAIRE |
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