| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| 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.
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