2012 Fiscal Year Final Research Report
Immune tolerant Fabry mouse by liver restricted expression become the inevitable material to study efficacy in enzyme replacement therapy with a modified .-N-acetylgalactosaminidase
| Project/Area Number |
22590373
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | 公益財団法人東京都医学総合研究所 (2012)
Tokyo Metropolitan Organization for Medical Research (2010-2011) |
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Principal Investigator |
TAJIMA Youichi 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (00300955)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWASHIMA Ikuo 公益財団法人東京都医学総合研究所, ゲノム医科学分野, 研究員 (40146824)
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| Project Period (FY) |
2010 – 2012
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| Keywords | ファブリー病 / 酵素補充療法 / 免疫寛容 / アナフィラキシー |
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| Research Abstract |
Previous studies have shown that modified human .-N-acetylgalactosaminidase (NAGA) with human .-galactosidase A (GLA)-like substrate specificity prevents globotriaosylceramide (Gb3) storage in Fabry model mouse. Furthermore, this modified NAGA is hardly expected to cause an allegic reaction in Fabry disease patients, it is highly promising as a new and safe enzyme for enzyme replacement therapy (ERT) for Fabry disease. Surprisingly, a modified NAGA intravenously injected into Fabry model mice was associated with a high rate of fatal anaphylaxis. Here, we reported that suppression of allegic reaction can be achieved in vivo by taking advantage of ability of the liver to promote immune tolerance. Expression of NAGA in the liver was accomplished stably in liver-specific NAGA transgenic (NAGA-Tg) Fabry model mice. Therefore, immune tolerant NAGA-Tg Fabry model mice could become the inevitable materials to study evaded immunity and enhanced efficacy in ERT with a modified NAGA.
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Research Products
(7 results)
