Development of a Novel Factor VIII Formulation Targeting Prevention of Inhibitor Development in Hemophilia A Therapy

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K17373
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Nara Medical University
• Principal Investigator: FURUKAWA Shoko 奈良県立医科大学, 医学部, 助教 (60596667)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 血友病A / インヒビター / 遺伝子解析

Outline of Final Research Achievements

The purpose of this study was to obtain basic data to elucidate the mechanism of inhibitor development through hematological and molecular cellular immunological analysis of mild/moderate hemophilia A patients with inhibitors. We had experience with seven cases by the beginning of the study period, and one new case occurred during the study period and could be analyzed. The point mutation in this case was E272K, and the one of 7 previous cases had the same mutation, suggesting that it may be a risk for the development of inhibitors. We also generated a mouse model of mild hemophilia A by knock-in of the P1777L mutation, which is highly homologous to P1809L in one of our own cases, and established the inhibitor generation and analysis model.

Free Research Field

血液凝固

Academic Significance and Societal Importance of the Research Achievements

本研究で解析できた新規症例では、過去にもインヒビター発生例のあった遺伝子変異が同定され、遺伝子変異がインヒビター発生リスクのひとつであるという過去の報告を支持する結果となった。また希少疾患である血友病A患者のうち軽症・中等症でインヒビターが発生する症例は少ないため、これまで十分な解析が不可能であったが、本研究で軽症血友病Aモデルマウスを作製しインヒビター解析系を確立できたことは、今後のインヒビター関連の解析に大いに役立つと考えられる。