Protein-anchoring therapy for mdx mouse model of duchenne muscular dystrophy

2016 Fiscal Year Final Research Report

• Project/Area Number: 25430049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Nagoya University
• Principal Investigator: Ito Mikako 名古屋大学, 医学系研究科, 助教 (60444402)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 筋ジストロフィー / AAV / Biglycan / mdx

Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is a devastating muscle disease caused by loss-of-function mutationsin DMD encoding dystrophin. Utrophin is a paralog ofdystrophin and is highly expressed at the neuromuscular junction. In mdx mice, utrophin is naturally
upregulated throughout the muscle fibers, which mitigates muscular dystrophy.
The protein-anchoring therapy was applied to mdx mice in this study. rAAV8 carrying hBGN encoding human biglycan was intravenously injected into 5-week-old mdx mice. The rAAV8-hBGN treatment improved motor deficits and decreased plasma creatine kinase activities. In muscle sections of treated mice, the number of central myonuclei and the distribution of myofiber sizes were improved. The low transduction efficiency and improved motor functions suggest that biglycan expressed in a small number of muscle fibers was likely to have been secreted and anchored to the cell surface throughout the whole muscular fibers.

Free Research Field

神経科学