Study on Mechano-Sensing Channel in muscular dystrophic dog

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: NAGATA Tetsuya 独立行政法人国立精神・神経医療研究センター, 神経研究所遺伝子疾患治療研究部, 室長 (50362976)
• Co-Investigator(Kenkyū-buntansha): TAKEDA Shin'ichi 独)国立精神・神経医療研究センター・神経研究所, 遺伝子疾患治療研究部, 部長 (90171644) ; IWATA Yuko 独立行政法人国立循環器病研究センター, 分子生理部, 室長 (80171908)
• Project Period (FY): 2010 – 2012
• Keywords: 神経分子病態学 / SAC / TRPfamily / TRPV2 / DMD

Research Abstract

A number of studies have reported the elevation of the cytosolic Ca2+ concentration in skeletal and cardiac muscles of muscular dystrophy. Chronic elevation of the cytosolic Ca2+ concentration could activate Ca2+-dependent cell signaling cascade and induce cell necrosis. The cellular mechanism for controlling Ca2+ influx in muscular dystrophy, however, is still unknown. The TRP channels form a large family of cation channels that likely function as tetramers in various processes, such as sensory signaling, most of which are permeable for Ca2+, and some also for Mg2+. To determine the relationship between TRP family and muscle degeneration, we analyzed the expression of TRP channel in skeletal and cardiac muscle of Canine models of Duchenne muscular dystrophy.

Research Products

• [Journal Article] Body-wide skipping of exons 45-55 in dystrophic mdx52mice by systemic antisense delivery (2012)
  • Author(s): Aoki Y, Yokota T, Nagata T, Nakamura A, Tanihata J, Saito T, Duguez M. R. S , Nagaraju K, Hoffman P. E, Partridge T, Takeda S
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Pages: 13763-13768,
  • DOI: doi: 10.1073/pnas.1204638109
  • Peer Reviewed
• [Journal Article] Extensive and prolonged restoration of dystrophin expression with vivo-morpholino-mediated multiple exon skipping in dystrophic dogs (2012)
  • Author(s): Yokota T, Nakamura A, Nagata T, Saito T, Kobayashi M, Aoki Y, Echigoya Y, Partridge T, Hoffman EP, Takeda S
  • Journal Title: Nucleic Acid Ther Volume: 22 Pages: 306-315
  • DOI: doi: 10.1089/nat.2012.0368
  • Peer Reviewed
• [Journal Article] Synthesis of 2'-O-[2-(N-Methylcarbamoyl)ethyl]ribonucl eosides Using Oxa-Michael reaction and chemical and biological properties of oligonucleotide derivatives incorporating these modified ribonucleosides. (2011)
  • Author(s): Yamada T, Okaniwa N, Saneyoshi H, Ohkubo A, Seio K, Nagata T, Aoki Y, Takeda S, Sekine M
  • Journal Title: J Org Chem Volume: 76 Pages: 3042-3053
  • DOI: doi: 10.1021/jo101963z
  • Peer Reviewed
• [Journal Article] In-frame dystrophin following exon 51-skipping improves muscle pathology and function in the exon 52-deficient mdx mouse (2010)
  • Author(s): Aoki Y, Nakamura A, Yokota T, Saito T, Okazawa H, Nagata T, Takeda S
  • Journal Title: Mol Ther Volume: 18 Pages: 1995-2005
  • DOI: doi:10.103 8/mt.2010.186
  • Peer Reviewed
• [Presentation] Exon skipping approach;exon 45-55 skipping (2012)
  • Author(s): Tetsuya Nagata
  • Organizer: 9th Japanese-French Symposium for `muscular dystrophy', Tokyo
  • Place of Presentation: Tokyo
  • Year and Date: 20120907-08
• [Presentation] Myogenic Transduction and Cell Surface Marker Selection of DMD Fibroblasts for Exon Skipping Assay. (2012)
  • Author(s): Saito T, Nagata T, Aoki Y, Tanihata J, Masuda S, Yokota T, Motohashi Y, Takeda S
  • Organizer: The 11th Annual Scientific meeting of The Asian Oceanian Myology Center
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2012-06-07
• [Presentation] Myogenic Transduction and Cell Surface Marker Selection of DMD Fibroblasts Stable Dystrophin mRNA Expression for Exon Skipping Assay (2012)
  • Author(s): Saito T, Nagata T, Aoki Y, Tanihata J, Masuda S, Yokota T, Shimizu-Motohashi Y, Takeda S
  • Organizer: American society of gene & cell therapy 15th Annual meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2012-05-17
• [Presentation] Demonstration of Systemic Exon 45-55 Multiple Skipping in Dystrophic mdx52 Mice (2012)
  • Author(s): Aoki Y, Nagata T, Nakamura A, Saito T, Tanihata J, Duguez S , Nagaraju K, Hoffman E, Partridge T, Yokota T, Takeda S
  • Organizer: American society of gene & cell therapy 15th Annual meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2012-05-16
• [Presentation] Mechanism of uptaking Morpholino into dystrophin-deficient muscle fibers (2011)
  • Author(s): Aoki Y, Nagata T, Yokota T, Takeda S
  • Organizer: American society of gene & cell therapy 14th Annual meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-05-20
• [Presentation] Challenges for antisense oligonucleotide based therapeutics, in particular for exon 51-skipping in Duchenne muscular dystrophy (2011)
  • Author(s): Aoki Y, Nagata T, Shimizu Y, Takeda S
  • Organizer: 4th International conference on modeling, simulation and applied optimization
  • Place of Presentation: Kuala Lumpur, Malaysia
  • Year and Date: 2011-04-21
• [Presentation] Skipping of exons 6 and 8 of the DMD gene has been achieved in myogenic cells from an exon-7 deleted DMD patient: direct application of antisense sequences found in study with canine muscular dystrophy (2010)
  • Author(s): Shimizu Y, Saito T, Aoki Y, Yokota T, Nagata T, Nakamura A, Osawa M, Takeda S
  • Organizer: 15th International Congress of World Muscle Society (WMS)
  • Place of Presentation: Kumamoto
  • Year and Date: 2010-10-15
• [Presentation] シンポジウムAntisense Oligos for Muscular Dystrophyアンチセンスオリゴを用いた筋ジストロフィーの治療 (2010)
  • Author(s): 永田哲也
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-21
• [Presentation] Feasibility and effectiveness of exon 51 skipping in human-like mdx mutation (2010)
  • Author(s): Aoki Y, Yokota T, Saito T, Nakamura A, Nagata T, Okazawa H, Takeda S
  • Organizer: American Society of Gene & Cell Therapy 13th Annual meeting
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-05-21
• [Book] The frontier of antisense oligonucleotide induced therapy (ed. by Takeda S). Fifty years of neuromuscular disorder research after discovery of creatine kinase as a diagnostic marker of muscular dystrophy (2011)
  • Author(s): Nagata T, Takeda S
  • Total Pages: 56-57
  • Publisher: IGAKU-SHOIN Ltd., Japan
• [Book] Challenges to oligonucleotides-based therapeutics, especially with regards to exon 51 skipping for Duchenne muscular dystrophy. Modeling, Simulation and Applied Optimization (ICMSAO) (2011)
  • Author(s): Aoki Y, Shimizu Y, Nagata T, Takeda S
  • Total Pages: 5775520
• [Book] 筋ジストロフィーの新しい治療戦略.神経内科 (2011)
  • Author(s): 永田哲也,武田伸一
  • Total Pages: 339-346
• [Patent(Industrial Property Rights)] アンチセンス核酸 (2010)
  • Inventor(s): 武田伸一,永田哲也ら
  • Industrial Property Rights Holder: 武田伸一,永田哲也ら
  • Industrial Property Number: 特願010-196032
  • Filing Date: 2010-09-01