Development of novel therapeutic method for ABC transporter-related diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: The University of Tokyo
• Principal Investigator: HAYASHI Hisamitsu 東京大学, 大学院薬学系研究科(薬学部), 助教 (10451858)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: ABCトランスポーター / 胆汁うっ滞症 / タンパク質分解

Outline of Final Research Achievements

Progressive familial intrahepatic cholestasis type 2 (PFIC2), a pediatric liver disease, is caused by mutations in ABCB11 encoding BSEP, an ABC transporter. No effective medical therapy has been established for PFIC2. Based on our previous findings from in vitro and animal studies, in this research project, we carried out clinical study to evaluate efficacy and safety of sodium phanylbutyrate (NaPB) in patients with PFIC2. Therapy with NaPB significantly improved biochemical tests and liver histology in the patients. Because this effect of NaPB involved inhibition of BSEP degradation, molecular mechanism underlying the degradation of BSEP and other ABC transporters was studied. A couple of molecules responsible for this mechanism have been identified.

Free Research Field

臨床薬理学