Targeting the TGF-beta type I receptor kinase as a molecular therapy for muscular dystrophy

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591013
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Kawasaki Medical School
• Principal Investigator: OHSAWA Yutaka Kawasaki Medical School, 医学部, 講師 (80246511)
• Co-Investigator(Kenkyū-buntansha): SUNADA Yoshihide 川崎医科大学, 医学部, 教授 (00240713) ; MURAKAMI Tatsufumi 川崎医科大学, 医学部, 准教授 (30330591)
• Project Period (FY): 2008 – 2010
• Keywords: 神経分子病態学

Research Abstract

Inhibitor targeting the TGF-β type I receptor kinase, recently developed for cancer, reverses impaired myoblast differentiation caused by myostatin, activin, and TGF-β1. Inhibitor ameliorated muscular atrophy in a caveolin-3-deficient muscular dystrophy model with decrease of p21, a target gene of the TGF-β, and with increase of satellite cells. Inhibitor thus could be a rational drug for muscular atrophy.

Research Products

• [Journal Article] Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice. (2011)
  • Author(s): Kawakami E, Kinouchi N, Adachi T, Ohsawa Y, Ishimaru N, Ohuchi H, Sunada Y, Hayashi Y, Tanaka E, Noji S
  • Journal Title: Dev Growth Differ. 53 Pages: 48-54
  • Peer Reviewed
• [Journal Article] Follistatin-derived peptide expression in muscle decreases adipose tissue mass and prevents hepatic steatosis. (2011)
  • Author(s): Nakatani M, Kokubo M, Ohsawa Y, Sunada Y, Tsuchida K
  • Journal Title: Am J Physiol Endocrinol Metab. 300 Pages: E543-E553
  • Peer Reviewed
• [Journal Article] Rapid screening for Japanese dysferlinopathy by fluorescent primer extension. (2010)
  • Author(s): Hayashi S, Ohsawa Y, Takahashi T, Suzuki N, Okada T, Rikimaru M, Murakami T, Aoki M, Sunada Y
  • Journal Title: Intern Med. 49 Pages: 2693-2696
  • Peer Reviewed
• [Journal Article] The transthyretin gene is expressed in Schwann cells of peripheral nerves. (2010)
  • Author(s): Murakami T, Ohsawa Y, Zhenghua L, Yamamura K, Sunada Y
  • Journal Title: Brain Res. 1348 Pages: 222-225
  • Peer Reviewed
• [Journal Article] Hereditary sensory ataxic neuropathy associated with proximal muscle weakness in the lower extremities. (2010)
  • Author(s): Murakami T, Fukai Y, Rikimaru M, Henmi S, Ohsawa Y, Sunada Y
  • Journal Title: J Neurol Sci. 291 Pages: 121-123
  • Peer Reviewed
• [Journal Article] Caveolin-3 regulates myostatin signaling. (2008)
  • Author(s): Ohsawa Y, Okada T, Kuga A, Hayashi S, Murakami T, Tsuchida K, Noji S, Sunada Y
  • Journal Title: Mini-review. Acta Myol. 27 Pages: 19-24
  • Peer Reviewed
• [Journal Article] The transthyretin gene is expressed in human and rodent dorsal root ganglia. (2008)
  • Author(s): Murakami T, Ohsawa Y, Sunada Y
  • Journal Title: Neurosci Lett. 436(3) Pages: 335-339
  • Peer Reviewed
• [Journal Article] Atelocollagen-mediated local and systemic applications of myostatin-targeting siRNA increase skeletal muscle mass. (2008)
  • Author(s): Kinouchi N, Ohsawa Y, Ishimaru N, Ohuchi H, Sunada Y, Hayashi Y, Tanimoto Y, Moriyama K, Noji S
  • Journal Title: Gene Ther. 15 Pages: 1126-1130
  • Peer Reviewed
• [Journal Article] Endoplasmic reticulum stress response in P104L mutant caveolin-3 transgenic mice.
  • Author(s): Kuga A, Ohsawa Y, Okada T, Kanda F, Kanagawa M, Toda T, Sunada Y
  • Journal Title: Hum Mol Genet. (in press)
  • Peer Reviewed
• [Presentation] Reprogrammed fibroblasts as a feasible source of cell-based therapy for muscular dystrophy. (2010)
  • Author(s): Ohsawa Y, Okada T, Fujii I, Nishimatsu S-I, Fujino M, Hayashi S, Rikimaru M, Murakami T, Nohno T, Sunada Y
  • Organizer: 15th International Congress of World Muscle Society
  • Place of Presentation: Kumamoto, Japan
  • Year and Date: 20101012-20101016
• [Presentation] Reprogrammed fibroblasts are a feasible source of cell therapy for caveolin-3-deficient and laminin α-2-deficient muscular dystrophy. (2010)
  • Author(s): Ohsawa Y, Fujii I, Okada T, Nishimatsu S, Hayashi S, Rikimaru M, Murakami T, Nohno T, Sunada Y
  • Organizer: 2010 FASEB Summer Research Conferences : Skeletal Muscle Satellite and Stem Cells
  • Place of Presentation: Carefee, Arizona, USA
  • Year and Date: 20100718-20100723
• [Presentation] Wound-healing MRL-MpJ phenotype improves outcome of dystrophin deficient mdx mice. (2010)
  • Author(s): Sunada Y, Ohsawa Y, Fujino M, Okada T, Hayashi S, Rikimaru M, Murakami T, Nishimatsu S, Nohno T, Nagao M
  • Organizer: XII International Congress on Neuromuscular Diseases
  • Place of Presentation: Naples, Italy
  • Year and Date: 20100718-20100721
• [Presentation] 筋ジストロフィーに対する抗myostatin治療薬の開発 (2010)
  • Author(s): 砂田芳秀、大澤裕、岡田只士、西松伸一郎、石崎雅俊、菅智宏、内野誠、濃野勉、野地澄晴、土田邦博
  • Organizer: 厚生労働省精神・神経疾患研究開発費「筋ジストロフィーおよびその関連疾患の分子病態解明、診断法確立と薬物治療の開発に関する研究」平成22年度「砂田班」班会議
  • Place of Presentation: 東京
  • Year and Date: 2010-12-03
• [Presentation] 筋ジストロフィーの分子病態 (2010)
  • Author(s): 砂田芳秀,大澤裕, ら
  • Organizer: 第28回日本神経治療学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2010-07-16
• [Presentation] nNOSはcaveolin-3欠損症の病態を抑制する. (2010)
  • Author(s): 砂田芳秀,大澤裕, ら
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-21
• [Presentation] 線維芽細胞のdirect reprogrammingによる筋ジストロフィーの細胞治療 (2010)
  • Author(s): 砂田芳秀、大澤裕、岡田只士、藤野雅広、力丸満惠、林紗織、村上龍文、藤井績
  • Organizer: 平成21年度厚生労働省精神・神経疾患研究委託費筋ジストロフィー総合班会議
  • Place of Presentation: 東京
  • Year and Date: 2010-01-09
• [Presentation] 線維芽細胞のdirect reprogrammingによる筋ジストロフィーの細胞治療 (2009)
  • Author(s): 砂田芳秀、大澤裕、岡田只士、藤野雅広、力丸満惠、林紗織、村上龍文、藤井績
  • Organizer: 厚生労働省精神・神経疾患研究委託費「筋ジストロフィーおよびその関連疾患の分子病態解明、診断法確立と薬物治療の開発に関する研究」平成21年度「砂田班」班会議
  • Place of Presentation: 東京
  • Year and Date: 2009-12-11
• [Presentation] Introduction of wound-healing MRL-MpJ phenotype improves skeletal muscle pathology in mdx mouse. (2009)
  • Author(s): Ohsawa Y, Fujino M, Okada T, Kuga A, Hayashi S, Rikimaru M, Sunada Y
  • Organizer: 14th International Congress of The World Muscle Society
  • Place of Presentation: Geneve, Switzerland
  • Year and Date: 2009-09-11
• [Presentation] TGF-βタイプIセリンスレオニンキナーゼ受容体阻害剤による筋ジストロフィー治療法の開発(第2報) (2009)
  • Author(s): 大澤裕、久我敦、林紗織、力丸満恵、村上龍文、砂田芳秀
  • Organizer: 第27回日本神経治療学会総会
  • Place of Presentation: 熊本
  • Year and Date: 2009-06-11
• [Presentation] A small-molecule inhibitor targeting transforming growth factor-b type receptor kinase ameliorate muscular atrophy in a mouse model of caveolin-3-deficient muscular dystrophy. (2008)
  • Author(s): Ohsawa Y, Okada T, Kuga A, Hayashi S, Murakami T, Sunada Y
  • Organizer: 13th International Congress of World Muscle Society
  • Place of Presentation: Newcastle, UK
  • Year and Date: 20080929-20081002
• [Presentation] cardiotoxin筋再生モデルにおけるcaveolin-3とdysferlinの動態 (2008)
  • Author(s): 久我敦、大澤裕、林紗織、村上龍文、砂田芳秀
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15
• [Presentation] caveolin-3欠損筋のdysferlin/myoferlin細胞内局在異常 (2008)
  • Author(s): 大澤裕、岡田只士、林紗織、久我敦、村上龍文、若山吉弘、澁谷誠二、砂田芳秀
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-15