Mannose receptor-mediated delivery of moss-made α-galactosidase A efficiently corrects enzyme deficiency in Fabry mice
| Autor: | Thomas Frischmuth, Holger Niederkrüger, Paulina Dabrowska-Schlepp, Andreas Schaaf, Andreas Busch, Jin-Song Shen, Taniqua S. Day, Xingli Meng, Raphael Schiffmann, Benjamin Fode, Chun I. Yu, Shuyuan Chen, Sabrina Forni |
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| Rok vydání: | 2015 |
| Předmět: |
Male
0301 basic medicine Mannose Receptors Cell Surface Pharmacology Kidney Endocytosis Receptor IGF Type 2 Cell Line Mice 03 medical and health sciences chemistry.chemical_compound Genetics Animals Humans Medicine Enzyme Replacement Therapy Lectins C-Type Genetics(clinical) Receptor Genetics (clinical) Cellular localization Mannosephosphates Alpha-galactosidase biology business.industry Enzyme replacement therapy medicine.disease Fabry disease Recombinant Proteins Isoenzymes Lysosomal Storage Diseases Mice Inbred C57BL Disease Models Animal Mannose-Binding Lectins 030104 developmental biology Biochemistry chemistry alpha-Galactosidase biology.protein Fabry Disease Female Original Article business Mannose Receptor Mannose receptor |
| Zdroj: | Journal of Inherited Metabolic Disease |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1007/s10545-015-9886-9 |
| Popis: | Enzyme replacement therapy (ERT) is an effective treatment for several lysosomal storage disorders (LSDs). Intravenously infused enzymes are taken up by tissues through either the mannose 6-phosphate receptor (M6PR) or the mannose receptor (MR). It is generally believed that M6PR-mediated endocytosis is a key mechanism for ERT in treating LSDs that affect the non-macrophage cells of visceral organs. However, the therapeutic efficacy of MR-mediated delivery of mannose-terminated enzymes in these diseases has not been fully evaluated. We tested the effectiveness of a non-phosphorylated α-galactosidase A produced from moss (referred to as moss-aGal) in vitro and in a mouse model of Fabry disease. Endocytosis of moss-aGal was MR-dependent. Compared to agalsidase alfa, a phosphorylated form of α-galactosidase A, moss-aGal was more preferentially targeted to the kidney. Cellular localization of moss-aGal and agalsidase alfa in the heart and kidney was essentially identical. A single injection of moss-aGal led to clearance of accumulated substrate in the heart and kidney to an extent comparable to that achieved by agalsidase alfa. This study suggested that mannose-terminated enzymes may be sufficiently effective for some LSDs in which non-macrophage cells are affected, and that M6P residues may not always be a prerequisite for ERT as previously considered. Electronic supplementary material The online version of this article (doi:10.1007/s10545-015-9886-9) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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