Searching for factors associated with progression and prognosis in patients with sporadic amyotrophic lateral sclerosis

• Project/Area Number: 25461277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Nagoya University
• Principal Investigator: Atsuta Naoki 名古屋大学, 医学部附属病院, 病院講師 (90547457)
• Co-Investigator(Kenkyū-buntansha): WATANABE Hirohisa 名古屋大学, 脳とこころの研究センター, 特任教授 (10378177) ; ITO Mizuki 名古屋大学, 医学部附属病院, 助教 (50437042) ; HIRAKAWA Akihiro 名古屋大学, 医学部附属病院, 講師 (90609330)
• Co-Investigator(Renkei-kenkyūsha): SOBUE Gen 名古屋大学, 大学院医学系研究科, 特任教授 (20148315) ; IIDA Aritoshi 理化学研究所, 統合生命医科学研究センター, 上級研究員 (10277585)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 筋萎縮性側索硬化症 / 疾患コホート / 予後因子 / 重症度スケール / 一塩基多型 / ゲノム遺伝子 / 遺伝子多型

Outline of Final Research Achievements

From analyses of a multicenter prospective amyotrophic lateral sclerosis (ALS) cohort data, we showed that age at onset was a common prognostic factor for both functional decline and survival in ALS patients. We also showed that age of onset had a significant influence on survival time and the progression of bulbar symptoms, but had no influence on upper limb function in sporadic ALS. We classified the patterns of functional decline in sporadic ALS patients and conducted an association study between the pattern and genome-wide single nucleotide polymorphisms (SNPs). We identified the following 4 clusters of longitudinal functional decline in the cases: a rapid decline cluster, an intermediate decline cluster, a sigmoidal decline cluster and a moderate decline cluster. We detected a linkage diseuilibrium (LD) block associated with a rapid functional decline in patients with sporadic ALS, which is linked to decreased expression of TTN.

Research Products

• [Journal Article] Age of onset differentially influences the progression of regional dysfunction in sporadic amyotrophic lateral sclerosis. (2016)
  • Author(s): Yokoi D, Atsuta N, Watanabe H, Nakamura R, Hirakawa A, Ito M, Watanabe H, Katsuno M, Izumi Y, Morita M, Taniguchi A, Oda M, Abe K, Mizoguchi K, Kano O, Kuwabara S, Kaji R, Sobue G; JaCALS.
  • Journal Title: J Neurol. Volume: Epub ahead of print
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. (2016)
  • Author(s): Watanabe H, Atsuta N, Hirakawa A, Nakamura R, Nakatochi M, Ishigaki S, Iida A, Sobue G.
  • Journal Title: Journal of Neurology, Neurosurgery & Psychiatry Volume: in press Pages: 851-8
  • DOI: 10.1136/jnnp-2015-311541
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Next-generation sequencing of 28 ALS-related genes in a Japanese ALS cohort (2016)
  • Author(s): Ryoichi Nakamura, Jun Sone, Naoki Atsuta, Genki Tohnai, Hazuki Watanabe, Daichi Yokoi, Masahiro Nakatochi, Hirohisa Watanabe, Mizuki Ito, Jo Senda, Masahisa Katsuno, Fumiaki Tanaka, Yuanzhe Li, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Osamu Kano, Masaya Oda, Satoshi Kuwabara, Koji Abe.
  • Journal Title: Neurobiol Aging. Volume: 39 Pages: 219-219
  • DOI: 10.1016/j.neurobiolaging.2015.11.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients. (2015)
  • Author(s): Watanabe H, Atsuta N, Nakamura R, Hirakawa A, Watanabe H, Ito M, Senda J, Katsuno M, Izumi Y, Morita M, Tomiyama H, Taniguchi A, Aiba I, Abe K, Mizoguchi K, Oda M, Kano O, Okamoto K, Kuwabara S, Hasegawa K, Imai T, Aoki M, Tsuji S, Nakano I, Kaji R, Sobue G.
  • Journal Title: Amyotroph Lateral Scler Frontotemporal Degener Volume: Epub ahead of print Pages: 230-236
  • DOI: 10.3109/21678421.2014.990036
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Prevalence and Incidence of Amyotrophic Lateral Sclerosis in Japan (2014)
  • Author(s): Doi Y, Atsuta N, Sobue G, Morita M, Nakano I.
  • Journal Title: Journal of Epidemiology Volume: 24 Issue: 6 Pages: 494-499
  • DOI: 10.2188/jea.je20140059 10.2188/jea.JE20140059
  • NAID: 130004678109
  • ISSN: 0917-5040, 1349-9092
  • Peer Reviewed / Open Access
• [Journal Article] Differential motor neuron involvement in progressive muscular atrophy: a comparative study with amyotrophic lateral sclerosis (2014)
  • Author(s): Riku Y, Atsuta N, Yoshida M, Tatsumi S, Iwasaki Y, Mimuro M, Watanabe H, Ito M, Senda J, Nakamura R, Koike H, Sobue G
  • Journal Title: BMJ Open Volume: 4
  • DOI: 10.1136/bmjopen-2014-005213
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Japanese and American ALS patient preferences regarding TIV (tracheostomy with invasive ventilation): A cross-national survey. (2014)
  • Author(s): Rabkin J, Ogino M, Goetz R, McElhiney M, Hupf J, Heitzman D, Heiman-Patterson T, Miller R, Katz J, Lomen-Hoerth C, Imai T, Atsuta N, Morita M, Tateishi T, Matsumura T, Mitsumoto H.
  • Journal Title: Amyotroph Lateral Scler Frontotemporal Degener. Volume: - Pages: 185-91
  • DOI: 10.3109/21678421.2014.896928
  • Peer Reviewed
• [Journal Article] 【神経疾患治療の進歩2013年】 運動ニューロン疾患の治療の進歩 (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Journal Title: 神経治療学 Volume: 31 Pages: 405-8
• [Journal Article] 病態解明・新規治療を目指した神経疾患の患者レジストリシステム(第1回) 筋萎縮性側索硬化症:JaCALS (2014)
  • Author(s): 熱田 直樹, 中村 亮一, 渡辺 はづき, 祖父江 元
  • Journal Title: BRAIN and NERVE: 神経研究の進歩 Volume: 66 Pages: 1090-6
  • NAID: 40020203407
• [Journal Article] 【痙性対麻痺】 痙性対麻痺で初発する筋萎縮性側索硬化症(ALS) (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Journal Title: 脊椎脊髄ジャーナル Volume: 27 Pages: 761-6
• [Journal Article] 【首下がり症候群】 筋萎縮性側索硬化症と首下がり (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Journal Title: 神経内科 Volume: 81 Pages: 57-61
• [Journal Article] 【神経系の慢性炎症】 神経変性疾患における慢性炎症 筋萎縮性側索硬化症(ALS) (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Journal Title: 別冊Bio Clinica: 慢性炎症と疾患 Volume: 3 Pages: 106-11
• [Journal Article] 【脊椎脊髄の科学-基礎と臨床の進歩Review 2014】 (第9章)保存療法 運動ニューロン疾患に対する治療法の開発 (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Journal Title: 脊椎脊髄ジャーナル Volume: 27 Pages: 445-50
• [Journal Article] Evaluation of SLC20A2 mutations that cause idiopathic basal ganglia calcification in Japan. (2014)
  • Author(s): Yamada, M., M. Tanaka, M. Takagi, S. Kobayashi, Y. Taguchi, S. Takashima, K. Tanaka, T. Touge, H. Hatsuta, S. Murayama, Y. Hayashi, M. Kaneko, H. Ishiura, J. Mitsui, N. Atsuta, G. Sobue, N. Shimozawa, T. Inuzuka, S. Tsuji and I. Hozumi
  • Journal Title: Neirology Volume: 82 Pages: 705-12
  • DOI: 10.1212/wnl.0000000000000143
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neck weakness is a potent prognostic factor in sporadic amyotrophic lateral sclerosis patients. (2013)
  • Author(s): Nakamura R, Atsuta N, Watanabe H, Hirakawa A, Watanabe H, Ito M, Senda J, Katsuno M, Tanaka F, Izumi Y, Morita M, Ogaki K, Taniguchi A, Aiba I, Mizoguchi K, Okamoto K, Hasegawa K, Aoki M, Kawata A, Abe K, Oda M, Konagaya M, Imai T, Nakagawa M, Tsuji S, Kaji R, Nakano I, Sobue G.
  • Journal Title: J Neurol Neurosurg Psychiatry. Volume: 84 Pages: 1365-1371
  • DOI: 10.1136/jnnp-2013-306020
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ERBB4 Mutations that Disrupt the Neuregulin-ErbB4 Pathway Cause Amyotrophic Lateral Sclerosis Type 19. (2013)
  • Author(s): Takahashi Y, Fukuda Y, Yoshimura J, Toyoda A, (33名省略）, Morishita S, Goto J and Tsuji S.
  • Journal Title: Am J Hum Genet. Volume: 93 Pages: 900-5
  • DOI: 10.1016/j.ajhg.2013.09.008
  • Peer Reviewed
• [Presentation] A rapid functional decline type of sporadic ALS is linked to low expression of TTN (2015)
  • Author(s): Naoki Atsuta, Hazuki Watanabe, Akihiro Hirakawa, Ryoichi Nakamura, Masahiro Nakatochi, Shinsuke Ishigaki, Aritoshi Iida, Shiro Ikegawa, Masahisa Katsuno, Yuishin Izumi, Mitsuya Morita, Akira Taniguchi, Koji Abe, Kouichi Mizoguchi, Osamu Kano, Takashi Imai, Masashi Aoki, Kenji Nakashima, Ryuji Kaji, Gen Sobue
  • Organizer: 26th International Symposium on ALS/MND
  • Place of Presentation: Orlando( USA)
  • Year and Date: 2015-12-12
  • Int'l Joint Research
• [Presentation] 我が国のALS患者に対する非侵襲的換気補助療法(NPPV)の転帰と予後 (2015)
  • Author(s): 熱田 直樹, 渡辺 はづき, 中村 亮一, 横井 大知, 渡辺 宏久, 伊藤 瑞規, 勝野 雅央, 和泉 唯信, 森田 光哉, 谷口 彰, 織田 雅也, 狩野 修, 溝口 功一, 阿部 康二, 桑原 聡, 梶 龍兒, 祖父江 元
  • Organizer: 第33回日本神経治療学会総会
  • Place of Presentation: 名古屋国際会議場(愛知県名古屋市)
  • Year and Date: 2015-11-27
• [Presentation] 教育講演「一歩進んだALS診療」いかに予後予測を行うか (2015)
  • Author(s): 熱田直樹、祖父江元
  • Organizer: 第56回日本神経学会学術大会
  • Place of Presentation: 朱鷺メッセ(新潟県新潟市)
  • Year and Date: 2015-05-21
  • Invited
• [Presentation] Factors affecting longitudinal functional decline and survival in amyotrophic lateral sclerosis patients (2014)
  • Author(s): Hazuki Watanabe, Naoki Atsuta, Ryoichi Nakamura, Akihiro Hirakawa, Hirohisa Watanabe, Mizuki Ito, Masahisa Katsuno, Yuishin Izumi, Mitsuya Morita, Hiroyuki Tomiyama, Akira Taniguchi, Koji Abe, Kouichi Mizoguchi, Osamu Kano, Satoshi Kuwabara, Takashi Imai, Masashi Aoki, Ryuji Kaji, Imaharu Nakano, Gen Sobue
  • Organizer: The 25th international symposium on ALS/MND
  • Place of Presentation: Brussels, Belgium,The Square, Brussels Meeting Centre
  • Year and Date: 2014-12-06
• [Presentation] ALSとFTLDの研究・治療の現在地を知る 分子病態からみたALSとFTLDの治療戦略 (2014)
  • Author(s): 熱田 直樹、祖父江 元
  • Organizer: 第32回日本神経治療学会総会
  • Place of Presentation: 東京都文京区(東京ドームホテル)
  • Year and Date: 2014-11-21
  • Invited
• [Presentation] ALSの進行を規定する因子の探索同定 (2014)
  • Author(s): 熱田直樹、渡辺はづき、中村亮一、平川晃弘、中杤昌弘、渡辺宏久、伊藤瑞規、千田譲、和泉唯信、梶龍兒、森田光哉、富山弘幸、谷口彰、溝口功一、狩野修、阿部康二、中野今治、飯田有俊、池川志郎、祖父江元
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡県福岡市(福岡国際会議場)
  • Year and Date: 2014-05-24
• [Presentation] ALSの進行を規定する因子の探索同定
  • Author(s): 熱田直樹、渡辺はづき、中村亮一、平川晃弘、中杤昌弘、渡辺宏久、伊藤瑞規、千田譲、和泉唯信、梶龍兒、森田光哉、富山弘幸、谷口彰、溝口功一、狩野修、阿部康二、中野今治、飯田有俊、池川志郎、祖父江元
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡国際会議場(福岡市)
• [Patent(Industrial Property Rights)] 急速進行型孤発性ALSの検査方法、検査キット、及び医薬のスクリーニング方法 (2015)
  • Inventor(s): 祖父江元、熱田直樹、渡邉はづき、平川晃弘、中杤昌弘
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-051093
  • Filing Date: 2015-03-13