Allele specific inhibition of mutant mRNA expression for repeat expansion disorders
| Project/Area Number |
15K15339
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Neurology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 筋強直性ジストロフィー / ハンチントン病 / リピート病 / トリプレットリピート / 脊髄小脳萎縮症 |
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| Outline of Final Research Achievements |
Repeat expansion disorders are caused by unstable expansions of tandem repeats, such as CAG or CTG. The transcripts containing the expanded repeat or abnormal protein products can give rise to a toxic gain-of-function by the mutant RNA (e.g. myotonic dystrophy) or mutant protein (e.g. Huntington disease). In this study, we identified small molecules that specifically inhibit transcription of mutant alleles with expanded repeats. These compounds reduced abnormal RNA levels in a cell model for myotonic dystrophy. The lead compound showed treatment effects in a mouse model for repeat expansion disorders. These results indicate that allele specific inhibition of mutant mRNA can be a means to treat repeat expansion disorders.
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| Academic Significance and Societal Importance of the Research Achievements |
リピート病は、そのほとんどが進行性の神経筋変性疾患であり、現在根本的な治療法がない難病である。本研究により、リピート病の原因を根源から断つ、新たな治療アプローチの可能性が示された。また、この治療アプローチは、リピート病のなかでも伸長リピート配列が同一の疾患群全てにおいて治療効果が期待できる。
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Report
(5 results)
Research Products
(48 results)
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[Journal Article] Myotonic dystrophy type 1 patient-derived iPSCs for the investigation of CTG repeat instability.2017
Author(s)
Ueki J, Nakamori M, Nakamura M, Nishikawa M, Yoshida Y, Tanaka A, Morizane A, Kamon M, Araki T, Takahashi MP, Watanabe A, Inagaki N, Sakurai H.
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Journal Title
Sci Rep.
Volume: 13
Issue: 1
Pages: 42522-42522
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.2016
Author(s)
Freyermuth F, Rau F, Kokunai Y, Linke T, Sellier C, Nakamori M, Kino Y,.......Zimmer T, Furling D, Takahashi MP, Charlet-Berguerand N.
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Journal Title
Nat Commun.
Volume: 7
Issue: 1
Pages: 11067-11067
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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