Comparative study of idursulfase beta and idursulfase in vitro and in vivo
| Autor: | Yo-Kyung Chung, Chihwa Kim, Eui-cheol Jo, Jinwook Seo, Jongmun Sohn, Byoung-Ju Lee, Hyi-Jeong Ji, Jaehyeon Lee |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Idursulfase Iduronate Sulfatase Pharmacology Biology Cell Line Glycosaminoglycan 03 medical and health sciences Mice In vivo Genetics Lysosomal storage disease medicine Animals Humans Enzyme Replacement Therapy Genetics (clinical) Glycoproteins Glycosaminoglycans Mucopolysaccharidosis II chemistry.chemical_classification Mice Knockout Hunter syndrome Enzyme replacement therapy medicine.disease In vitro Mice Inbred C57BL 030104 developmental biology Enzyme chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Original Article medicine.drug |
| Zdroj: | Journal of Human Genetics |
| ISSN: | 1435-232X |
| Popis: | Hunter syndrome is an X-linked lysosomal storage disease caused by a deficiency in the enzyme iduronate-2-sulfatase (IDS), leading to the accumulation of glycosaminoglycans (GAGs). Two recombinant enzymes, idursulfase and idursulfase beta are currently available for enzyme replacement therapy for Hunter syndrome. These two enzymes exhibited some differences in various clinical parameters in a recent clinical trial. Regarding the similarities and differences of these enzymes, previous research has characterized their biochemical and physicochemical properties. We compared the in vitro and in vivo efficacy of the two enzymes on patient fibroblasts and mouse model. Two enzymes were taken up into the cell and degraded GAGs accumulated in fibroblasts. In vivo studies of two enzymes revealed similar organ distribution and decreased urinary GAGs excretion. Especially, idursulfase beta exhibited enhanced in vitro efficacy for the lower concentration of treatment, in vivo efficacy in the degradation of tissue GAGs and improvement of bones, and revealed lower anti-drug antibody formation. A biochemical analysis showed that both enzymes show largely a similar glycosylation pattern, but the several peaks were different and quantity of aggregates of idursulfase beta was lower. |
| Databáze: | OpenAIRE |
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