Therapeutic application of PEG-DAO in chronic granulomatous disease

Research Project

Project/Area Number	21791016
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Pediatrics
Research Institution	Sojo University
Principal Investigator	NAKAMURA Hideaki Sojo University, 薬学部, 助手 (30435151)
Project Period (FY)	2009 – 2010
Project Status	Completed (Fiscal Year 2010)
Budget Amount *help	¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000) Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000) Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords	小児感染症学 / PEG-DAO / 感染症 / 慢性肉芽腫 / FAD / 活性酸素
Research Abstract	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.