2018 Fiscal Year Final Research Report
Treatment with Polyethylene Glycol-Conjugated Fungal d-Amino Acid Oxidase Reduces Lung Inflammation in a Mouse Model of Chronic Granulomatous Disease
| Project/Area Number |
16K09972
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Miyazaki |
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Principal Investigator |
Nunoi Hiroyuki 宮崎大学, 医学部, 元教授 研究生 (50218260)
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| Co-Investigator(Kenkyū-buntansha) |
前田 浩 崇城大学, DDS研究所, 特任教授 (90004613)
松倉 誠 崇城大学, 薬学部, 教授 (70238997)
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| Research Collaborator |
Maeda Hiroshi 崇城大学, DDS研究所, 特任教授 (90004613)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | PEG-DAO酵素補充療法 / CGDマウス / カンジダ死菌誘発性肺炎 / D型アミノ酸 |
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| Outline of Final Research Achievements |
Chronic granulomatous disease (CGD) is a primary immunodeficiency wherein phagocytes are unable to produce reactive oxygen species (ROS) owing to a defect in the NADPH oxidase complex. Patients with CGD experience bacterial and fungal infections and excessive inflammatory disorders. Bone marrow transplantation and gene therapy are theoretically curative, however, residual pathogenic components cause inflammation and/or organic damage in patients. In this study, the efficacy of the ROS-generating enzyme replacement therapy was tested with PEG-fDAO using three experimental strategies with the in vivo lung inflammation model of gp91phox-knockout CGD mice. The lung weight and pathological findings suggest the condition was ameliorated by administration PEG-fDAO, followed by intraperitoneal injection of d-phenylalanine or d-proline. These data reveal the targeted delivery of PEG-fDAO and show that PEG-fDAO can be used to treat inflammation in CGD in vivo.
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| Free Research Field |
先天性免疫不全症 好中球機能異常症
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| Academic Significance and Societal Importance of the Research Achievements |
慢性肉芽腫症（CGD）は活性酸素産性能の欠損により、殺菌能が低下するために、激しい感染症を繰り返す疾患である。これまで、骨髄移植や遺伝子治療が成功を収めつつあるが、患者状態の悪い場合は前処置の問題など非常なリスクを伴うことが問題であった。我々は、炎症局所で過酸化水素を産生できるPEG化したD-アミノ酸オキシダーゼ(PEG-pDAO)を用いた酵素補充療法をCGD患者好中球を用いたin vitroでの有用性を証明してきた。今回カンジダ死菌で誘発されたCGDマウス肺炎モデルを用いて新たに開発したPEG-fDAOのin vivoでの有用性を確認し、CGDの新たな酵素補充療法による治療法を提示した。
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