徳島大学 教育・研究者情報データベース(EDB)

1. (英) Tajima Youichi

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2. (英) Kawashima Ikuo

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3. (英) Tsukimura Takahiro

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4. (英) Sugawara Kanako

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5. (英) Kuroda Mayuko

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6. (英) Suzuki Toshihiro

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7. (英) Togawa Tadayasu

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8. (英) Chiba Yasunori

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9. (英) Jigami Yoshifumi

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10. (英) Ohno Kazuki

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11. (英) Fukushige Tomoko

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12. (英) Kanekura Takuro

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13. 伊藤 孝司

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14. (英) Ohashi Toya

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15. (英) Sakuraba Hitoshi

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(英) Use of a Modified alpha-N-Acetylgalactosaminidase in the Development of Enzyme Replacement Therapy for Fabry Disease

(英) A modified alpha-N-acetylgalactosaminidase (NAGA) with alpha-galactosidase A (GLA)-like substrate specificity was designed on the basis of structural studies and was produced in Chinese hamster ovary cells. The enzyme acquired the ability to catalyze the degradation of 4-methylumbelliferyl-alpha-D-galactopyranoside. It retained the original NAGA's stability in plasma and N-glycans containing many mannose 6-phosphate (M6P) residues, which are advantageous for uptake by cells via M6P receptors. There was no immunological cross-reactivity between the modified NAGA and GLA, and the modified NAGA did not react to serum from a patient with Fabry disease recurrently treated with a recombinant GLA. The enzyme cleaved globotriaosylceramide (Gb3) accumulated in cultured fibroblasts from a patient with Fabry disease. Furthermore, like recombinant GLA proteins presently used for enzyme replacement therapy (ERT) for Fabry disease, the enzyme intravenously injected into Fabry model mice prevented Gb3 storage in the liver, kidneys, and heart and improved the pathological changes in these organs. Because this modified NAGA is hardly expected to cause an allergic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for ERT for Fabry disease.

1. (英) Amino Acid Substitution
2. (英) Animals
3. (英) Binding Sites
4. (英) CHO Cells
5. (英) Catalysis
6. (英) Cells, Cultured
7. (英) Cricetinae
8. (英) Cricetulus
9. (英) Culture Media, Conditioned
10. (英) DNA, Complementary
11. (英) Disease Models, Animal
12. (英) Drug Stability
13. (英) Enzyme Replacement Therapy
14. (英) Fabry Disease
15. (英) Fibroblasts
16. (英) Fluorescent Dyes
17. (英) Galactosides
18. (英) Genetic Vectors
19. (英) Humans
20. (英) Hydrogen-Ion Concentration
21. (英) Hymecromone
22. 免疫組織化学(immunohistochemistry)
23. (英) Kidney
24. (英) Liver
25. (英) Mice
26. (英) Mice, Knockout
27. (英) Models, Molecular
28. 分子量(molecular weight)
29. 心筋(myocardium)
30. (英) Recombinant Proteins
31. (英) Retroviridae
32. (英) Transfection
33. (英) Trihexosylceramides
34. (英) alpha-N-Acetylgalactosaminidase

1. (英) Article.Affiliation: Department of Clinical Genetics, Meiji Pharmaceutical University, Tokyo 204-8588, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

4. (英) OtherID: PMC2775840