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Research of signal transduction system in antisense therapy for muscular dystrophy

Research Project

Project/Area Number 20591223
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKobe University

Principal Investigator

TAKESHIMA Yasuhiro  Kobe University, 大学院・医学研究科, 特命教授 (40281141)

Co-Investigator(Kenkyū-buntansha) MATSUO Masafumi  神戸大学, 医学研究科, 教授 (10157266)
YAGI Mariko  神戸大学, 医学研究科, 助教 (60362787)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアンチセンスオリゴヌクレオチド / 筋ジストロフィー / シグナル伝達因子 / エクソンスキッピング / 筋ジストロフー / NF-κB
Research Abstract

We have shown the clinical effectiveness of antisense therapy for Duchenne muscular dystrophy (DMD) which converts out-of-frame to in-frame mutation by inducing the exon skipping by antisense oligonucleotide. To enhance the effect of this therapy, we developed the in vitro model system of antisense therapy based on the mutation spectrum of Japanese DMD cases. Furthermore, the effect of antisense oligonucleotide on dystrophin production and signal transduction system was investigated. The effect of this therapy was different among DMD cases, and it is important to examine the effect of antisense therapy using individual in vitro system of each case.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2010 2009 2008

All Journal Article (20 results) (of which Peer Reviewed: 9 results) Presentation (16 results)

  • [Journal Article] Molecular characterization of the 5'-UTR of retinal dystrophin reveals a cryptic intron that regulates translational activity.2010

    • Author(s)
      Kubokawa I, Takeshima Y, Ota M, Enomoto M, Okizuka Y, Mori T, Nishimura N, Awano H, Yagi M, Matsuo M.
    • Journal Title

      Mol Vis. 16

      Pages: 2590-2597

    • Related Report
      2010 Final Research Report
  • [Journal Article] Contemporary retrotransposition of a novel non-coding gene induces exon-skipping in dystrophin mRNA.2010

    • Author(s)
      Awano H, Malueka RG, Yagi M, Okizuka Y, Takeshima Y, Matsuo M.
    • Journal Title

      J Hum Genet. 55

      Pages: 785-790

    • NAID

      10030737817

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center.2010

    • Author(s)
      Takeshima Y, Yagi M, Okizuka Y, Awano H, Zhang Z, Yamauchi Y, Nishio H, Matsuo M.
    • Journal Title

      J Hum Genet. 55

      Pages: 379-388

    • NAID

      10030735518

    • Related Report
      2010 Final Research Report
  • [Journal Article] Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD.2010

    • Author(s)
      Okizuka Y, Takeshima Y, Itoh K, Zhang Z, Awano H, MarMarrar, Mar, Marma K, Kumagai T, Yagi M, Matsuo M.
    • Journal Title

      BMC Med Genet. 30

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutation spectrum of the dystrophin gene in 442 Duchenne/Becker muscular dystrophy cases from one Japanese referral center.2010

    • Author(s)
      Takeshima Y
    • Journal Title

      Journal of Human Genetics.

      Volume: 55 Pages: 379-388

    • NAID

      10030735518

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Low incidence of limb-girdle muscular dystrophy type 2C revealed by a mutation study in Japanese patients clinically diagnosed with DMD.2010

    • Author(s)
      Okizuka Y
    • Journal Title

      BMC Medical Genetics.

      Volume: 11 Pages: 49-49

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4.2010

    • Author(s)
      Dwianingsih EK
    • Journal Title

      Molecular Genetics and Metabolism.

      Volume: 101 Pages: 233-237

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insertion of the IL1RAPL1 gene into the duplication junction of the dystrophin gene.2009

    • Author(s)
      Zhang Z, Yagi M, Okizuka Y, Awano H, Takeshima Y, Matsuo M.
    • Journal Title

      J Hum Genet. 54

      Pages: 466-473

    • NAID

      10030731391

    • Related Report
      2010 Final Research Report
  • [Journal Article] Small mutations detected by multiplex ligation-dependent probe amplification of the dystrophin gene.2009

    • Author(s)
      Okizuka Y, Takeshima Y, Awano H, Zhang Z, Yagi M, Matsuo M.
    • Journal Title

      Genet Test Mol Biomarkers. 13

      Pages: 427-431

    • Related Report
      2010 Final Research Report
  • [Journal Article] In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G-->A mutations in introns of the dystrophin gene.2009

    • Author(s)
      Habara Y, Takeshima Y, Awano H, Okizuka Y, Zhang Z, Saiki K, Yagi M, Matsuo M.
    • Journal Title

      J Med Genet. 46

      Pages: 542-547

    • Related Report
      2010 Final Research Report
  • [Journal Article] In vitro splicing analysis showed that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G→A mutations in introns of the dystronhin gene2009

    • Author(s)
      Habara Y
    • Journal Title

      Journal of Medical Genetics 46

      Pages: 542-547

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Small mutations detected by multiplex ligation-dependent probe amplification of the dystrophin gene2009

    • Author(s)
      Okizuka Y
    • Journal Title

      Genetic Testing and Molecular Biomarkers 13

      Pages: 427-431

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Insertion of the IL1RAPL1 gene into the duplication junction of the dystrophin gene2009

    • Author(s)
      Zhang Z
    • Journal Title

      Journal of Human Genetics 54

      Pages: 466-473

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High incidence of electrocardiogram abnormalities in young patients with duchenne muscular dystrophy.2008

    • Author(s)
      Takami Y, Takeshima Y, Awano H, Okizuka Y, Yagi M, Matsuo M.
    • Journal Title

      Pediatr Neurol. 39

      Pages: 399-403

    • Related Report
      2010 Final Research Report
  • [Journal Article] Dystrophin nonsense mutations can generate alternative rescue transcripts in lymphocytes.2008

    • Author(s)
      Nishiyama A, Takeshima Y, Zhang Z, Habara Y, Tran TH, Yagi M, Matsuo M.
    • Journal Title

      Ann Hum Genet. 72

      Pages: 717-724

    • Related Report
      2010 Final Research Report
  • [Journal Article] Tandem duplications of two separate fragments of the dystrophin gene in a patient with Duchenne muscular dystrophy.2008

    • Author(s)
      Zhang Z, Takeshima Y, Awano H, Nishiyama A, Okizuka Y, Yagi M, Matsuo M.
    • Journal Title

      J Hum Genet. 53

      Pages: 215-219

    • NAID

      10021248166

    • Related Report
      2010 Final Research Report
  • [Journal Article] A strong exonic splicing enhancer in dystrophin exon 19 achieve proper splicing without an upstream polypyrimidine tract.2008

    • Author(s)
      Habara Y, Doshita M, Hirozawa S, Yokono Y, Yagi M, Takeshima Y, Matsuo M.
    • Journal Title

      J Biochem. 143

      Pages: 303-310

    • NAID

      10024908594

    • Related Report
      2010 Final Research Report
  • [Journal Article] High incidence of electrocardiogram abnormalities in young patients with duchenne muscular dystrophy.2008

    • Author(s)
      Takami Y
    • Journal Title

      Pediatr Neurol. 39

      Pages: 399-403

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dystrophin nonsense mutations can generate alternative rescue transcripts in lymphocytes.2008

    • Author(s)
      Nishiyama A
    • Journal Title

      Ann Hum Genet 72

      Pages: 717-724

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tandem duplications of two separate fragments of the dystrophingene in a patient with Duchenne muscular dystrophy.2008

    • Author(s)
      Zhang Z
    • Journal Title

      J Hum Genet. 53

      Pages: 215-219

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Chemical treatment of muscular dystrophy that enhances skipping of the mutated exon in the dystrophin gene.2010

    • Author(s)
      Nishida A, Kataoka N, Takeshima Y, Yagi M, Awano H, Ota M, Itoh K, Hagiwara M, Matsuo M.
    • Organizer
      The American Society of Human Genetics 60th Annual Meeting.
    • Place of Presentation
      Washigton, DC.
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutation spectrum of the dystrophin gene in 456 Duchienne/Becker muscular dystrophy cases from one Japanese referral center.2010

    • Author(s)
      Takeshima Y, Yagi M, Ota M, Awano H, Yamauchi Y, Malueka RG, Dwianingsih EK, Nishio H, Matsuo M.
    • Organizer
      15th International Congress of The World Muscle Society.
    • Place of Presentation
      Kumamoto.
    • Related Report
      2010 Final Research Report
  • [Presentation] Antisense RNA/ethylene-bridged nucleic acids chimera induces exon 45 skipping and restores dystrophin expression in myocytes of Duchenne muscular dystrophy.2010

    • Author(s)
      Yagi M, Ota M, Awano H, Takeshima Y, Matsuo M.
    • Organizer
      15th International Congress of The World Muscle Society.
    • Place of Presentation
      Kumamoto
    • Related Report
      2010 Final Research Report
  • [Presentation] Antisense RNA/ENA chimera against dystrophin exon 45 leads exon 45 skipping followed by dystrophin expression in cells from duchenne muscular dystrophy.2010

    • Author(s)
      Yagi M, Takeshima Y, Awano H, Ota M, Malueka RG, Dwianingsih EK, Nishida A, Lee T, Matsuo M.
    • Organizer
      6th Annual Meeting of the Oligonucleotide Therapeutics Society.
    • Place of Presentation
      Southern California
    • Related Report
      2010 Final Research Report
  • [Presentation] Long-term administration of antisense oligonucleotide against dystrophin exon 19 for the treatment of Duchenne muscular dystrophy with exon 20 deletion.2010

    • Author(s)
      Matsuo M, Takeshima Y, Yagi M, Awano H.
    • Organizer
      XII International Congress on Neuromusular Diseases.
    • Place of Presentation
      Naples.
    • Related Report
      2010 Final Research Report
  • [Presentation] Antisense RNA/ethylene- bridged nucleic acid chimera induces exon 45 skipping and restores dystrophin expression in DMD muscle cells.2010

    • Author(s)
      Yagi M, Ota M, Awano H, Takeshima Y, Matsuo M.
    • Organizer
      XII International Congress on Neuromusular Diseases.
    • Place of Presentation
      Naples.
    • Related Report
      2010 Final Research Report
  • [Presentation] Genotype-phenotype correlation of the dystrophinopathy cases with small mutations in the dystrophin gene.2010

    • Author(s)
      Awano H, Takeshima Y, Yagi M, Yamauchi Y, Malueka RG, Dwianingsih EK, Matsuo M.
    • Organizer
      Pediatric Academic Societies' 2010 Annual Meeting.
    • Place of Presentation
      Vancouver.
    • Related Report
      2010 Final Research Report
  • [Presentation] 培養筋細胞におけるアンチセンスオリゴヌクレオチドによるエクソン45のスキッピング誘導率は変異によって異なる2010

    • Author(s)
      八木麻理子
    • Organizer
      第52回日本小児神経学会総会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Duchenne 型筋ジストロフィー分子治療の適応に関する検討2009

    • Author(s)
      竹島泰弘
    • Organizer
      第51回日本小児神経学会総会
    • Place of Presentation
      米子コンベンションセンター(鳥取県)
    • Year and Date
      2009-05-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Antisense RNA/ethylene-bridged nucleic acids chimera induces exon skipping and restores dystrophin expression in myocytes of Duchenne muscular dystrophy.2009

    • Author(s)
      Yagi M, Yamauchi Y, Awano H, Takeshima Y, Matsuo M.
    • Organizer
      The American Society of Human Genetics 59th Annual Meeting.
    • Place of Presentation
      Hawaii.
    • Related Report
      2010 Final Research Report
  • [Presentation] In vitro splicing analysis reveals that availability of a cryptic splice site is not a determinant for alternative splicing patterns caused by +1G>A mutations in introns of the dystrophin gene.2009

    • Author(s)
      Matsuo M, Habara Y, Takeshima Y, Awano H, Okizuka Y, Zhang Z, Yagi M.
    • Organizer
      14th International Congress of The World Muscle Society.
    • Place of Presentation
      Geneva.
    • Related Report
      2010 Final Research Report
  • [Presentation] High incidence of outlier from the reading-frame rule in dystrophinopathy patients with duplication mutations in the dystrophin gene.2009

    • Author(s)
      Yagi M, Awano H, Okizuka Y, Takeshima Y, Matsuo M.
    • Organizer
      Pediatric Academic Societies' 2009 Annual Meeting.
    • Place of Presentation
      Baltimore.
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutation spectrum of the dystrophin gene in 433 Japanese dystrophinopathy cases.2008

    • Author(s)
      Takeshima Y, Yagi M, Okizuka Y, Awano H, Zang Z, Saiki K, Matsuo M.
    • Organizer
      The American Society of Human Genetics 58th Annual Meeting.
    • Place of Presentation
      Philadelphia.
    • Related Report
      2010 Final Research Report
  • [Presentation] Splicing errors casued by small mutations in the dystrophin gene are different between lymphocytes and muscle tissues.2008

    • Author(s)
      Okizuka Y, Awano H, Yagi M, Takeshima Y, Matsuo M.
    • Organizer
      Pediatric Academic Societies' 2008 Annual Meeting.
    • Place of Presentation
      Hawaii.
    • Related Report
      2010 Final Research Report
  • [Presentation] A novel retrotransposon that was recently inserted into exon 67 of the dystrophin gene.2008

    • Author(s)
      Awano H, Yagi M, Okizuka Y, Zhang Z, Takeshima Y, Matsuo M.
    • Organizer
      Joint 7th Human Genome Organization (HUGO)-Pacific Meeting and the 8th Asia-Pacific Conference on Human Genetics.
    • Place of Presentation
      Cebu.
    • Related Report
      2010 Final Research Report
  • [Presentation] Mutation spectrum of the dystrophin gene in 433 Japanese dystrophinopathy cases.2008

    • Author(s)
      Takeshima Y
    • Organizer
      The American Society of Human Genetics 58th Annual Meeting
    • Place of Presentation
      Philadelphia, USA
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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