Exhaustive analysis for clinical application of anti-complement drugs

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: Ueda Yasutaka 大阪大学, 医学系研究科, 特任助教(常勤) (30533848)
• Co-Investigator(Kenkyū-buntansha): 西村 純一 大阪大学, 医学系研究科, 助教 (80464246) ; 金倉 譲 大阪大学, 医学系研究科, 教授 (20177489)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 発作性夜間ヘモグロビン尿症 / PNH / 補体 / 溶血性貧血 / 抗補体薬

Outline of Final Research Achievements

Eculizumab, an anti-C5 antibody, effectively blocks complement-mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria (PNH), but some patients show poor response to the drug, and others show insufficient recovery from hemolytic anemia possibly due to extravascular hemolysis manifested by eculizumab. We obtained new candidate drugs for PNH including an anti-C5 recombinant protein secreted in tick saliva, an anti-C5 circular peptide, a Factor D inhibitor, C1-inactivator, and a C3 inhibitor, and tested, in vitro, those efficacy in inhibiting intravascular and extravascular hemolysis. Our data suggest that targeting a molecule in the alternative pathway may be promising in its potency and safety in treating PNH.

Free Research Field

血液および腫瘍内科学