Animal study for evaluating the effect of meclozine on FGFR3 signaling

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10439
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Nagoya University
• Principal Investigator: Matsushita Masaki 名古屋大学, 医学部附属病院, 病院助教 (60721115)
• Co-Investigator(Kenkyū-buntansha): 鬼頭 浩史 名古屋大学, 医学系研究科, 准教授 (40291174) ; 三島 健一 名古屋大学, 医学系研究科, 寄附講座助教 (40646519) ; 杉浦 洋 名古屋大学, 医学部附属病院, 医員 (40750477)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 軟骨無形成症 / FGFR3 / 低身長 / メクロジン / 骨密度 / 骨質 / 大後頭孔

Outline of Final Research Achievements

Achondroplasia (ACH) is characterized by short stature associated with severe complications such as stenoses of foramen magnum and spinal canal due to the gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3). We have already found that meclozine, an anti-histamine drug that has long been used for motion sickness, inhibited FGFR3 signaling. In the current study, the 1 or 2 mg/kg/day of meclozine increased the bone length of 7-day-old Ach mice for 10 days, but did not rescue the foramen magnum stenosis. Meclozine administration would be commenced immediately after birth since the synchondroses around the foramen magnum was closed at the age of 4.5 days. On the other hand, the 1 or 2 mg/kg/day of meclozine increased the bone volume and bone mineral density in addition to the bone length in growing Ach mice.

Free Research Field

整形外科