Development of therapeutic drugs for fibrodysplasia ossificans progressiva by drug repositioning strategies

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K15548
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Kitoh Hiroshi 名古屋大学, 医学系研究科, 准教授 (40291174)
• Co-Investigator(Kenkyū-buntansha): 杉浦 洋 名古屋大学, 医学部附属病院, 医員 (40750477) ; 松下 雅樹 名古屋大学, 医学部附属病院, 病院助教 (60721115)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 進行性骨化性線維異形成症 / ドラッグ・リポジショニング / 異所性骨化 / Id1 / ALK2

Outline of Final Research Achievements

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by progressive heterotopic ossification in various extraskeletal sites. FOP is caused by a gain-of-function mutation in ALK2, which causes up regulation of a transcriptional factor, Id1. We screened FDA-approval drugs for suppression of the Id1 promoter activated by the mutant ALK2 in C2C12 myogenic cells. We found that azelastine HCl (anti-histamine), Fluvastatin sodium salt (ant-hyperlipidemia), and Trimipramine maleate salt (anti-depressant) suppressed the Id1 promoter activity in a dose-dependent manner. These drugs also downregulated the expressions of the Id1-target osteoblastic genes such as alkaline phosphatase and osteocalcin.

Free Research Field

整形外科学