Identification of the most appropriate therapeutic target for PNH

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54010:Hematology and medical oncology-related
• Research Institution: Osaka University
• Principal Investigator: Ueda Yasutaka 大阪大学, 医学系研究科, 助教 (30533848)
• Co-Investigator(Kenkyū-buntansha): 西村 純一 大阪大学, 医学系研究科, 招へい教授 (80464246) ; 高森 弘之 大阪大学, 医学部附属病院, 医員 (80792077)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 発作性夜間ヘモグロビン尿症 / PNH / 溶血性貧血 / 抗補体薬 / 血管内溶血 / 血管外溶血 / プロペルジン

Outline of Final Research Achievements

Anti-C5 antibodies effectively blocks complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), but some patients show poor response to the antibodies due to extravascular hemolysis manifested under anti-C5 treatment. Properdin is a component of the complement alternative pathway, and we found that anti-properdin antibody alone blocked hemolysis of PNH red blood cells, and hindered accumulation of C3 on the red blood cells in vitro, suggesting that the antibody blocks both intra- and extravascular hemolysis. The blood level of properdin was stably comparatively low in PNH patients. The antibody didn’t interfere with the classical and lectin pathways, suggesting it might mitigate the infectious risk in the patients under treatment. Those data suggest that blocking complement components consisting of the alternative pathway, especially properdin, may be one of the most appropriate therapeutic targets for PNH.

Free Research Field

溶血性貧血

Academic Significance and Societal Importance of the Research Achievements

稀少疾患であるPNH患者に対して様々な新規治療薬が臨床開発中であるが、どの薬剤が患者にとって最適なのかはまだ分かっていない。今回の研究を通じて、PNHの新規治療薬の方向性として第2経路阻害が有望であることが明らかとなり、今後PNHの治療薬選択を考える上での重要な知見が得られた。