Resarch on novel therapeutic molecular target for Duchenne muscular dystrophy that inhibits titin-degrading enzymes

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07845
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52050:Embryonic medicine and pediatrics-related
• Research Institution: Kobe University
• Principal Investigator: Hiroyuki Awano 神戸大学, 医学研究科, 准教授 (30437470)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Duchenne型筋ジストロフィー / カルパイン

Outline of Final Research Achievements

The dystrophin-deficient muscle of Duchenne muscular dystrophy has muscle breakdown, however, the pathophysiology has been unclear. In this study, we considered that calpain, a proteolytic enzyme, is associated with muscle breakdown, and investigated its expression. Using patient-derived myoblasts, frozen muscle, etc., the expression of calpain 1 and 2 and calpastatin, which is an endogenous inhibitory protein of calpain, were compared with healthy subjects by real-time PCR or Western blotting. The ratio of calpain 1 and 2 to calpastatin expression in DMD muscle samples was higher than in healthy subjects. It was clarified that the expression of calpain and its inhibitory protein was unbalanced in dystrophin-deficient muscle.

Free Research Field

筋疾患

Academic Significance and Societal Importance of the Research Achievements

Duchenne型筋ジストロフィー(DMD)患者のジストロフィン欠損筋のカルパイン１およびカルパイン２の発現が、阻害タンパクであるカルパスタチンに比して増加していた。これはカルパインがDMD患者の筋崩壊の病態に関連することを示唆する結果である。また、DMDの筋崩壊を阻止する根治治療の標的分子の同定に寄与する結果であると考えられる。