Development of the therapy for Duchenne muscular dystrophy targeting MMP-9

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860792
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Shinshu University
• Principal Investigator: SHIBA Naoko 信州大学, 医学部附属病院, 特任研究員 (00639289)
• Research Collaborator: NAKAMURA Akinori 信州大学, 医学部附属病院, 教授 (10303471) ; MIYAZAKI Daigo 信州大学, 医学部附属病院, 講師 (80596370) ; FUKUSHIMA Kazuhiro 信州大学, 医学部附属病院, 特任准教授 (10421835) ; YOSHIZAWA Takahiro 信州大学, 学術研究院医学系, 助教 (40713392)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: ジストロフィン / MMP-9 / MCP-1 / MIP-2 / オステオポンチン

Outline of Final Research Achievements

We investigated the effect of genetic ablation of MMP-9 in the mdx mouse model (mdx/Mmp9-/-). At the early disease stage, the muscles of mdx/Mmp9-/- mice showed reduced necrosis and neutrophil invasion, accompanied by down-regulation of chemokine MIP-2. In addition, muscle regeneration was enhanced, which coincided with increased macrophage infiltration and upregulation of MCP-1, and resulted in increased muscle strength. The mdx/Mmp9-/- mice also displayed accelerated upregulation of osteopontin expression in skeletal muscle at the acute onset phase of dystrophy. However, at a later disease stage, the mice exhibited increased fibroadipose tissue. These results showed that MMP-9 might have multiple functions during disease progression. Therapy targeting MMP-9 may improve muscle pathology and function at the early disease stage, but continuous inhibition of this protein may result in the accumulation of fibroadipose tissues and reduced muscle strength at the late disease stage.

Free Research Field

筋ジストロフィー