Therapeutic application of PEG-DAO in chronic granulomatous disease

PEG-DAO在慢性肉芽肿性疾病中的治疗应用

• 批准号: 21791016
• 负责人: NAKAMURA Hideaki
• 金额: $ 2.66万
• 依托单位: Sojo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791016/
• 关键词: 小児感染症学; PEG-DAO; 感染症; 慢性肉芽腫; FAD; 活性酸素

We found that DAO shows bactericidal activity through hydrogen peroxide or hypohalous acid produced by coordinative function with myeloperoxidase in vitro. Furthermore DAO activity deficient mouse showed increased susceptibility of infection against staphylococcus aureus. We further investigated the possible application of DAO for chronic granulomatous disease (CGD) which is caused by loss of hydrogen peroxide production. For this purpose, we developed pegylated DAO, which has directionality toward infection site or inflammatory site by enhanced permeability and retention (EPR) effect without loss of enzymatic acitivity. Treatment of PEG-DAO to CGD neutrophils recovered its bactericidal function, and abolished by inhibition of myeloperoxidase. In conclusion DAO is one of the antibacterial enzyme in our body by producing the hydrogen peroxide. Furthermore its supplementation by PEG-DAO will may recover the bactericidal acitivty of CGD neutrophils.

我们发现DAO通过在体外与脊髓过氧化物酶协调性功能产生的过氧化氢或低钙化酸显示杀菌活性。此外，DAO活性缺乏小鼠表现出增加对金黄色葡萄球菌感染的敏感性。我们进一步研究了DAO在慢性肉芽肿性疾病（CGD）中的可能应用，这是由于过氧化氢损失引起的。为此，我们开发了DAO，它通过增强的渗透性和保留效应（EPR）效应而不会丧失酶促效率，从而对感染部位或炎症部位具有方向性。将PEG-DAO治疗到CGD嗜中性粒细胞恢复了其杀菌功能，并通过抑制脊髓过氧化物酶消除了。总之，DAO是我们体内通过产生过氧化氢的抗菌酶之一。此外，通过PEG-DAO补充其补充可能会恢复CGD中性粒细胞的杀菌性杀菌性。

项目成果

Intracellular uptake of water soluble ZnPP micells (SMA-ZnPP and PEG-ZnPP) and the unique release mechanism of the drug from the micelles.

水溶性ZnPP胶束（SMA-ZnPP和PEG-ZnPP）的细胞内摄取以及药物从胶束中的独特释放机制。

• 发表时间: 2010

Intracellular uptake of water soluble ZnPP micelles (SMA-ZnPP and PEG-ZnPP) and the unique release mechanism of the drug from their micelles.

水溶性 ZnPP 胶束（SMA-ZnPP 和 PEG-ZnPP）的细胞内摄取以及药物从其胶束中的独特释放机制。

• 发表时间: 2010
• 作者: 吉田路子;今村俊彦;中谷拓也;福原正太;藤木敦;平嶋良章;細井創;田村真一;石田宏之;中村秀明
• 通讯作者: 中村秀明