2013 Fiscal Year Final Research Report
Investigation of fibrotic factors during the exon-skipping therapy using antisense oligonucleotide for muscular dystrophy
Project/Area Number |
23591495
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Pediatrics
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Research Institution | Kobe University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
YAGI Mariko 神戸大学, 大学院医学研究科, 研究員 (60362787)
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Project Period (FY) |
2011 – 2013
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Keywords | アンチセンスオリゴヌクレオチド / 筋ジストロフィー / エクソンスキッピング / 線維化因子 |
Research Abstract |
To enhance the effectiveness of antisense oligonucleotide (AO)-mediated exon skipping therapy for Duchenne muscular dystrophy (DMD), the relationship of fibrosis and inflammation to DMD was examined. At the beginning pharmacodynamics of the AO inducing the skipping of exon 45(AO85) was examined using cell-free splicing system, and the EC50 of AO85 was revealed to be 58.0 nM. Then, urinary tetranor PGDM which is major urinary metabolite of prostaglandin (PG) D2 were shown to be increased in DMD patients and became higher with advancing age. It was indicated that PGD2-mediated inflammation plays a role in the pathology of DMD. Furthermore, administration of AO85 to DMD cases resulted in the improvement of some inflammatory cytokines. These results indicated that fibrosis and inflammation were involved in the pathogenesis of DMD, and the modification of these factors was considered as one possible strategy for the enhancement of the effectiveness of AO-mediated exon skipping therapy.
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[Journal Article] Utility of transmural myocardial strain profile for prediction of early left ventricular dysfunction in patients with Duchenne muscular dystrophy2013
Author(s)
Yamamoto T, Tanaka H, Matsumoto K, Lee T, Awano H, Yagi M, Imanishi T, Hayashi N, Takeshima Y, Kawai H, Kawano S, and Hirata K
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Journal Title
Am J Cardiol
Volume: 111
Pages: 902-7
Peer Reviewed
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[Presentation] Three-dimensional gait analysis of Duchenne muscular dystrophy; a trial to evaluate the therapeutic effect of RNA/ENA chimera antisense oligonucleotide that induces dystrophin exon 45 skipping2013
Author(s)
Takeshima Y, Yagi M, Lee T, Kusunoki N, Ojima I, Minami S, Asai T, Nakagawa A, Iijima K, and Matsuo M
Organizer
18th International Congress of the World Muscle Society
Place of Presentation
California, USA
Year and Date
20131001-05
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[Presentation] A prostaglandin D2 metabolite is elevated in the urine samples of patients with Duchenne muscular dystrophy2013
Author(s)
Nakagawa T, Takeuchi A, Kakiuchi R, Lee T, Yagi M, Awano H, Iijima K, Takeshima Y, Urade Y, and Matsuo M
Organizer
18th International Congress of the World Muscle Society
Place of Presentation
California, USA
Year and Date
20131001-05
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[Presentation] A small chemical, TG003, enhances skipping of mutated dystrophin exons : the third example revealing a decrease of exonic splicing enhancer density in common2012
Author(s)
Nishida A, Takeshima Y, Kataoka N, Yagi M, Awano H, Lee T, Iijima K, Hagiwara M, and Matsuo M
Organizer
The American Society of Human Genetics, the 62^<nd> Annual Meeting
Place of Presentation
San Francisco, USA
Year and Date
20121106-10
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