Screening for small chemicals that induces skipping of exon in the dystrophin gene.

2015 Fiscal Year Final Research Report

• Project/Area Number: 26860803
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kobe Gakuin University
• Principal Investigator: Nishida Atsushi 神戸学院大学, 総合リハビリテーション学部, 研究員 (80640987)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: Duchenne型筋ジストロフィー / エクソンスキッピング / スプライシング操作

Outline of Final Research Achievements

Duchenne muscular dystrophy (DMD) is a common inherited muscle disease caused by a mutation in the dystrophin gene. In our previous report, we showed a possibility of DMD therapy using a small chemical kinase inhibitor TG003, via enhancing a nonsense mutated exon skipping. In this study, we tried to find superior small chemicals. As a result of screening, we found that cycloheximide (CHX) has the exon skipping activity, moreover CHX enhanced the exon skipping synergistically with TG003. However, CHX is not suitable for clinical use for its toxicity. Then, we tested other compounds that have been reported to modify the splicing, and found staurosporine (STS), a kinase inhibitor. STS was shown to enhance mutated exon skipping more efficiently compared to TG003. Furthermore, STS was shown to increase the dystrophin protein expression in the immortalized cells derived from DMD patient’s muscle. CHX and STS could be nominated as candidates for leading compounds.

Free Research Field

分子生物学