Basic research aiming for developing anti-disseminated intravascular coagulation drug targeting for complement

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K18962
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Meijo University
• Principal Investigator: Mizuno Tomohiro 名城大学, 薬学部, 助教 (40711669)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 補体第5因子 / 播種性血管内凝固症候群

Outline of Final Research Achievements

Disseminated intravascular coagulation (DIC) is seen in patients with systemic inflammation. In this study, we used DIC model animal induced by extracellular histones to screen new therapeutic agents. We focused on the cross-talk between complement and coagulation system, and investigated whether an anti-complement drug ameliorated DIC. Complement component 5a (C5a) receptor antagonist ameliorated liver injury in DIC. Heparin and chondroitin sulfate (CS) are linear polysaccharides, and its negative charge allows binding to extracellular histones. Our study elucidated that the interaction between CS and extracellular histones did not affect coagulation system in DIC.

Free Research Field

医療系薬学

Academic Significance and Societal Importance of the Research Achievements

播種性血管内凝固症候群（DIC）は、重篤な感染症やがん患者で発症する疾患であり、その死亡率は高いことが知られています。我々は、DICの新規治療薬を開発するため、補体系の機能を調節する薬物と、DICの原因物質である細胞外ヒストンを中和する薬物の有効性について、実験動物を用いて検討しました。どちらの薬物もDICの症状を緩和することが明らかになり、有望な新規治療薬となりうることが示唆されました。今後、臨床応用に向け、更なる検討を進めていく予定です。