Establishment of antibody drug on non-alcoholic steatohepatitis through Met signaling.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09411
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: University of Toyama
• Principal Investigator: Takahara Terumi 富山大学, 医学部, 教授 (60240777)
• Co-Investigator(Kenkyū-buntansha): 梨井 康 国立研究開発法人国立成育医療研究センター, 移植免疫研究室, 室長 (60321890)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: HGF / Met / 抗体医薬 / NASH / 再生医療

Outline of Final Research Achievements

HGF receptor Met makes a hybrid with insulin receptor and acts as a regulator for insulin sensitivity in the liver. The present study tried to establish new antibody drug therapy for NASH using Met-activating antibody. Treatment with Met-activating antibody on STAM mice (NASH model) did not show the significant decreased blood sugar or fatty liver, compared with control. However, treatment with Met-activating antibody on hepatectomized cirrhotic liver showed significant recovery of fibrosis, inflammation and regeneration and this effects continuedfor long period. Met-activating antibody can be used as an antibody drug for organ regeneration.

Free Research Field

消化器病学

Academic Significance and Societal Importance of the Research Achievements

dbdbマウスではMet作動性抗体を投与したところ血糖値、脂肪肝の改善を認めることからMet 作動性抗体はNASH治療に有効と考えられる。一方で肝硬変の肝切除モデルでは抗体投与群で著明な線維化・炎症の改善、肝再生の促進を認め、その効果は長く持続した。Met作動性抗体は抗体医薬としての安定性を示し、HGFが持つ多彩な作用を考えると、NASHのみならず幅広い組織修復・再生療法に有効である。