Characterization of the von Willebrand factor/factor VIII complex produced by a novel purification process
| Autor: | Baik Lin Seong, So Ra Kim, You Jin Jung, Eun Sun Chang, Suk Hoon Ha, Jee Won Ahn |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Coagulation protein congenital hereditary and neonatal diseases and abnormalities animal diseases Pharmacology toxicology Hemophilia A law.invention Mice 03 medical and health sciences 0302 clinical medicine Von Willebrand factor law hemic and lymphatic diseases von Willebrand Factor Drug Discovery Von Willebrand disease medicine Animals Humans Purification methods Factor VIII Dose-Response Relationship Drug biology Chemistry Organic Chemistry medicine.disease Molecular biology Mice Inbred C57BL Molecular Weight Disease Models Animal Drug Combinations 030104 developmental biology 030220 oncology & carcinogenesis cardiovascular system Recombinant DNA biology.protein Molecular Medicine circulatory and respiratory physiology |
| Zdroj: | Archives of Pharmacal Research. 43:714-723 |
| ISSN: | 1976-3786 0253-6269 |
| Popis: | Factor VIII (FVIII) is a blood coagulation protein that circulates as a complex with von Willebrand factor (vWF) in the plasma. In the survey of inhibitors in plasma product exposed toddlers (SIPPET) study, plasma-derived FVIII containing vWF was less immunogenic in hemophilia A patients than products with only high-purity FVIII only or recombinant FVIII. The FVIII purified by the conventional purification process using anion-exchange (AEX) chromatography had a low vWF content. In this study, purified vWF was added to the purified FVIII to increase the vWF content. The purified vWF was recovered from the discarded washing solution of the AEX chromatography using cation-exchange (CEX) chromatography. The vWF/FVIII complex had an abundance of high molecular weight vWF similar to the normal plasma, and a low reactivity of FVIII inhibitors. Furthermore, its efficacy was observed in a mouse model of hemophilia A. Therefore, the vWF/FVIII complex produced by our new purification method could be an effective and less immunogenic therapeutic agent for the hemophilia A and von Willebrand disease. |
| Databáze: | OpenAIRE |
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