Development of gene and cell therapy for muscular dystrophies.

• Project/Area Number: 24591284
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: National Center of Neurology and Psychiatry
• Principal Investigator: KIMURA En 独立行政法人国立精神・神経医療研究センター, トランスレーショナルメディカルセンター, 室長 (60433025)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 筋ジストロフィー / 遺伝子治療 / レンチウイルスベクター / 幹細胞移植 / 幹細胞移植治療 / 再生医療

Outline of Final Research Achievements

Series of Lentiviral vectors were prepared; each carrying different-type of full- and short-version of dystrophin, marker gene, myogenic transcriptional factors, under the control of various combinations of muscle specific promoters and the miR target sequences. The myoD-ER(T), fusion gene with myoD and modified estrogen receptor biding domain for Tamoxifen, was successfully introduced into dermal fibroblasts by lentiviral transduction, and covert themselves to myogenic cells. These cell therapy resources are candidates of genetic modifications by not only viral vectors based technologies and newly developed gene-editing technologies.

Research Products

• [Journal Article] The TREAT-NMD DMD Global Database: Analysis of More than 7,000 Duchenne Muscular Dystrophy Mutations. (2015)
  • Author(s): 1)Bladen CL, Salgado D, Monges S, Foncuberta ME, …, Kimura E, …, Bushby K, Verschuuren J, Aartsma-Rus A, Beroud C, Lochmuller H.
  • Journal Title: Hum mutat. Volume: 36 Issue: 4 Pages: 395-402
  • DOI: 10.1002/humu.22758
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Nationwide patient registry for GNE myopathy in Japan. (2014)
  • Author(s): Mori-Yoshimura M, Hayashi YK, Yonemoto N, Nakamura H, Murata M, Takeda S, Nishino I, Kimura E.
  • Journal Title: Orphanet J Rare Dis. Volume: 9 Issue: 1 Pages: 150-150
  • DOI: 10.1186/s13023-014-0150-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The infrastructure for the clinical research of muscular dystrophies: Remudy and MDCTN (2014)
  • Author(s): 木村 円, 中村治雅, 三橋里美, 竹内芙実, 森まどか, 清水玲子, 小牧宏文, 林由起子, 西野一三, 川井 充, 武田伸一
  • Journal Title: Rinsho Shinkeigaku Volume: 54 Issue: 12 Pages: 1069-1070
  • DOI: 10.5692/clinicalneurol.54.1069
  • NAID: 130004921235
  • ISSN: 0009-918X, 1882-0654
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prednisolone improves walking in Japanese Duchenne muscular dystrophy patients (2013)
  • Author(s): Takeuchi F, Yonemoto N, Nakamura H, Shimizu R, Komaki H, Mori-Yoshimura M, Hayashi YK, Nishino I, Kawai M, Kimura E, Takeda S
  • Journal Title: J Neurol Volume: 260 Issue: 12 Pages: 3023-3029
  • DOI: 10.1007/s00415-013-7104-y
  • Peer Reviewed
• [Journal Article] The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia. (2013)
  • Author(s): Bladen CL, Rafferty K, ..., Kimura E, ..., Lochmuller H.
  • Journal Title: Hum mutat. Volume: 34(11) Issue: 11 Pages: 1449-1457
  • DOI: 10.1002/humu.22390
  • Peer Reviewed
• [Journal Article] Characteristics of Japanese Duchenne and Becker muscular dystrophy patients in a novel Japanese national registry of muscular dystrophy (Remudy). (2013)
  • Author(s): Nakamura H, Kimura E†, Mori-Yoshimura M, Komaki H, Matsuda Y, Goto K, Hayashi YK, Nishino I, Takeda SI, Kawai M.
  • Journal Title: Orphanet J Rare Dis. Volume: 8(1) Issue: 1 Pages: 60-60
  • DOI: 10.1186/1750-1172-8-60
  • Peer Reviewed
• [Journal Article] Optineurin is potentially associated with TDP-43 and involved in the pathogenesis of inclusion body myositis. (2013)
  • Author(s): Yamashita S., Kimura E., Tawara N., Sakaguchi H., Nakama T., Maeda Y., Hirano T., Uchino M., & Ando Y.
  • Journal Title: Neuropathol. Appl. Neurobiol. Volume: 39 Issue: 4 Pages: 406-416
  • DOI: 10.1111/j.1365-2990.2012.01297.x
  • Peer Reviewed
• [Journal Article] Muscle biopsy findings predictive of malignancy in rare infiltrative dermatomyositis (2013)
  • Author(s): Uchino M, Yamashita S, Uchino K, Mori A, Hara A, Suga T, Hirahara T, Koide T, Kimura E, Yamashita T, Ueda A, Kurisaki R, Suzuki J, Honda S, Maeda Y, Hirano T, Ando Y
  • Journal Title: Clin Neurol Neurosurg Volume: 115(5) Issue: 5 Pages: 603-6
  • DOI: 10.1016/j.clineuro.2012.07.019
  • Peer Reviewed
• [Journal Article] Efficient and reproducible myogenic differentiation from human iPS cells: prospects for modeling Miyoshi Myopathy in vitro. (2013)
  • Author(s): Tanaka, A., et al
  • Journal Title: PLoS ONE Volume: 8(4) Issue: 4 Pages: e61540-e61540
  • DOI: 10.1371/journal.pone.0061540
  • Peer Reviewed
• [Journal Article] Heatstroke in patients with Parkinson's disease (2012)
  • Author(s): Satoshi Yamashita
  • Journal Title: Neurological Sciences Volume: 33 Issue: 3 Pages: 685-687
  • DOI: 10.1007/s10072-011-0842-7
  • Peer Reviewed
• [Journal Article] Significant CMAP decrement by repetitive nerve stimulation is more frequent in median than ulnar nerves of patients with amyotrophic lateral sclerosis (2012)
  • Author(s): Satoshi Yamashita, Hideya Sakaguchi, Akira Mori
  • Journal Title: Muscle Nerve Volume: 45 Issue: 3 Pages: 426-428
  • DOI: 10.1002/mus.22301
  • NAID: 120005123115
  • Peer Reviewed
• [Journal Article] Long-term outcome of polymyositis treated with high single-dose alternate-day prednisolone therapy (2012)
  • Author(s): Makoto Uchino
  • Journal Title: European Neurology Volume: 68 Issue: 2 Pages: 117-121
  • DOI: 10.1159/000338474
  • Peer Reviewed
• [Journal Article] Myasthenic crisis patients who require intensive care unit management (2012)
  • Author(s): Hideya Sakaguchi
  • Journal Title: Muscle and Nerve Volume: 46 Issue: 3 Pages: 440-442
  • DOI: 10.1002/mus.23445
  • Peer Reviewed
• [Journal Article] The association between dermatomyositis and papillary thyroid cancer: a case report. (2012)
  • Author(s): Ikeda T, Kimura E, Hirano T, Uchino M
  • Journal Title: Rheumatol Int. Volume: 32(4) Issue: 4 Pages: 959-61
  • DOI: 10.1007/s00296-010-1763-0
  • Peer Reviewed
• [Presentation] Remudy, Japanese national registry for neuromuscular diseases, as a clinical utility model for various rare disease registries with international harmonization (2015)
  • Author(s): Kimura E, Nakamura H, Mitsuhashi S, Mori-Yoshimura M, Takahashi PM, Takeuchi F, Wu S, Zheng Y, Matsumura T, Komaki H, Nishino I, Kawai M, Dawkins H, Béroud C, Lochmüller H, Takeda S, and Remudy Muscular Dystrophy Clinical Research Group
  • Organizer: 14th AOMC Annual Scientific Meeting
  • Place of Presentation: Shangri-La Hotel, Bangkok, Thailand
  • Year and Date: 2015-03-01 – 2015-03-04
• [Presentation] 患者登録システム, Remudy – の意義 (2014)
  • Author(s): 木村 円
  • Organizer: 第1回筋ジストロフィー医療研究会
  • Place of Presentation: 国立病院機構講堂, 東京
  • Year and Date: 2014-10-24 – 2014-10-25
  • Invited
• [Presentation] National registry of Japanese dystrophinopathy patients: Remudy (2014)
  • Author(s): Takeuchi F, Nakamura H, Mitsuhashi S, Mori-Yoshimura M, Hayashi YK, Shimizu R, Komaki H, Nishino I, Kawai M, Takeda S, Kimura E.
  • Organizer: 19th International WMS Congress
  • Place of Presentation: the Academic Center of Berlin, in the Langenbeck-Virchow-Haus, Berlin, Germany
  • Year and Date: 2014-10-07 – 2014-10-11
• [Presentation] DMD/BMD patient registry in Japan: Remudy (2014)
  • Author(s): Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Takeuchi F, Shimizu R, Komaki H, Nishino I, Kawai M, Takeda S
  • Organizer: 13th International Congress on Neuromuscular Diseases ICNMD
  • Place of Presentation: Acroplis Convention Centre, Nice, France
  • Year and Date: 2014-07-05 – 2014-07-10
• [Presentation] 筋ジストロフィーの臨床開発を推進する研究基盤：RemudyとMDCTN (2014)
  • Author(s): 木村 円, 中村治雅, 三橋里美, 竹内芙実, 森まどか, 清水玲子, 小牧宏文, 林由起子, 西野一三, 川井 充, 武田伸一
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場, 福岡
  • Year and Date: 2014-05-21 – 2014-05-24
  • Invited
• [Presentation] The CARE-NMD survey in Japan, (2013)
  • Author(s): Kimura E.
  • Organizer: The CARE-NMD International Conference on DMD
  • Place of Presentation: Hilton Westend,Budapest, Hangary
  • Invited
• [Presentation] Neuromuscular disease Registry (2013)
  • Author(s): Kimura E.
  • Organizer: 第一回上海DMDトランスレーショナル医学と健康介護シンポジューム
  • Place of Presentation: Children's Hosital of Fudan University 上海, 中国
  • Invited
• [Presentation] Current status of dystrophinopathy patient registry in Japan: Remudy. (2013)
  • Author(s): Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Takeuchi F, Shimizu R, Komaki H, Nishino I, Kawai M, Takeda S
  • Organizer: The 18th International Congress of the World Muscle Society
  • Place of Presentation: Asilomar Conference Grounds,California,USA
• [Presentation] Current status of patient registration in Japan: REMUDY - Infrastructure for new drug development to treat muscular dystrophy (2013)
  • Author(s): Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Takeuchi F, Shimizu R, Komaki H, Nishino I, Kawai M, Takeda S
  • Organizer: The 12th Annual Scientific Meeting of the Asian and Oceanian Myology Center (AOMC)
  • Place of Presentation: Sofitel Xi'an on Renmin Square Xi’an, China
• [Presentation] 希少疾患レジストリー：国際協調と臨床開発における役割 ー Remudyの現状と目指すもの (2013)
  • Author(s): 木村 円
  • Organizer: 第34回日本臨床薬理学会学術総会
  • Place of Presentation: 東京国際フォーラム（東京）
  • Invited
• [Presentation] Remudy・DMD/BMD患者情報登録の現状 (2013)
  • Author(s): 木村 円, 林由起子, 森まどか, 清水玲子, 小牧宏文, 西野一三, 川井 充, 武田伸一
  • Organizer: 第54回日本神経学会学術大会
  • Place of Presentation: 東京国際フォーラム（東京）
• [Presentation] INFRASTRUCTURE FOR NEW DRUG DEVELOPMENT TO TREAT MUSCULAR DYSTROPHY - CURRENT STATUS OF PATIENT REGISTRATION IN JAPAN: REMUDY. (2012)
  • Author(s): Kimura, E, Nakamura H, Hayashi YK, Mori MY, Komaki H, Nishino I, Kawai M, Takeda S
  • Organizer: ICORD 2012
  • Place of Presentation: 東京大学 駒場リサーチキャンパス コンベンション・ホール
• [Presentation] DMD/BMD 登録制度. (2012)
  • Author(s): 木村 円
  • Organizer: 2012国际DMD康复与治疗大会暨第一届DMD医患大会
  • Place of Presentation: 北京, 中国General Hospital of Chinese Armed Police Force
  • Invited
• [Presentation] Exciting developments in the Japanese neuromuscular field (2012)
  • Author(s): Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Komaki H, Shimizu R, Ogata K, Matsumura T, Takahashi MP, Takada H, Nishino I, Kawai M, Takeda S
  • Organizer: 6th TREAT-NMD Curators’ & 5th TGDOC Meeting
  • Place of Presentation: Istanbul, Turkey Kalyon Hotel Sahilyolu
  • Invited
• [Presentation] Infrastructure for new drug development to treat muscular dystrophy-Current status of patient registration in japan:Remudy (2012)
  • Author(s): Kimura E, Nakamura H, Hayashi YK, Mori-Yoshimura M, Shimizu R, Komaki H, Nishino I, Kawai M, Takeda S
  • Organizer: 17th International Congress of the World Muscle Society
  • Place of Presentation: Perth, Australia The Perth Convention and Exhibition Center
• [Book] Clinical Neuroscience (2015)
  • Author(s): 木村 円
  • Publisher: 中外医学社
• [Book] BRAIN and NERVE (2014)
  • Author(s): 木村 円, 中村治雅, 西野一三
  • Publisher: 医学書院
• [Book] 今日の神経疾患治療指針 第2版 (2013)
  • Author(s): 木村円, 武田伸一
  • Total Pages: 1100
  • Publisher: 医学書院
• [Book] 中外医学社 (2013)
  • Author(s): 木村円
  • Total Pages: 206
  • Publisher: 中外医学社
• [Book] 今日の神経疾患治療指針 第2版 進行性筋ジストロフィー（ジストロフィノパチー） (2013)
  • Author(s): 木村円, 武田伸一
  • Total Pages: 1100
  • Publisher: 医学書院
• [Book] 筋疾患のみかた，考えかた Remudyによる患者登録 (2013)
  • Author(s): 木村円
  • Total Pages: 820
  • Publisher: 中外医学社
• [Remarks] Remudy
  • URL: http://www.remudy.jp
• [Remarks] 国立精神・神経医療研究センター トランスレーショナル・メディカルセンター
  • URL: http://www.ncnp.go.jp/tmc/
• [Remarks] 神経・筋疾患患者情報登録 Remudy
  • URL: http://www.remudy.jp