Development of a novel therapeutic approach for ALS using anti-TNF antibody

2013 Fiscal Year Final Research Report

• Project/Area Number: 23659458
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: The University of Tokushima
• Principal Investigator: KAJI Ryuji 徳島大学, ヘルスバイオサイエンス研究部, 教授 (00214304)
• Co-Investigator(Kenkyū-buntansha): GOTO Satoshi 徳島大学, 大学院ヘルスバイオサイエンス研究部, 特任教授 (50240916)
• Co-Investigator(Renkei-kenkyūsha): KAWARAI Toshitaka 徳島大学, 大学院ヘルスバイオサイエンス研究部, 講師 (50614137)
• Project Period (FY): 2011 – 2013
• Keywords: ＴＮＦα / ＡＬＳ / ＳＯＤ１

Research Abstract

Mouse anti-TNF alpha antibody was intraperitoneally administered to SOD1 mice, which are widely used for animal model for amyotrophic lateral sclerosis. We physiologically and pathologically evaluated the efficacy of the therapy or suppression of disease progression. No significant result was obtained in physiological evaluations, including life span, body weight and motor functions. However, pathological examination revealed partial ameliorative response, including the numbers of survival motor neurons and the reactive gliosis. These results further supported involvement of neuroinflammation in motor neuron death by mutant SOD1 probably at the end stage. Evaluation of the downstream cascades, such as NF kappa, JNK-AP-1 and caspase 3, is necessary to optimize the therapy using the anti-TNF alpha antibody.

Research Products

• [Journal Article] The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) (2012)
  • Author(s): Hiroyuki Ishiura, Wataru Sako, Mari Yoshida, Toshitaka Kawarai, Osamu Tanabe, Jun Goto, Yuji Takahashi, Hidetoshi Date, Jun Mitsui, Budrul Ahsan, Yaeko Ichikawa, Atsushi Iwata, Hiide Yoshino, Yuishin Izumi, Koji Fujita, Kouji Maeda, Satoshi Goto, Hidetaka Koizumi, Ryoma Morigaki, Masako Ikemura, Naoko Yamauchi, Shigeo Murayama, Garth A. Nicholson, Hidefumi Ito, Gen Sobue, Masanori Nakagawa, Ryuji Kaji and Shoji Tsuji
  • Journal Title: Am J Hum Genet Volume: 91 Pages: 320-329
  • DOI: 10.1016/j.ajhg.2012.07.014
  • Peer Reviewed
• [Journal Article] ALS-parkinsonism-dementia complex of Kii and other related diseases in Japan (2012)
  • Author(s): Kaji R, Izumi Y, Adachi Y, Kuzuhara S
  • Journal Title: Parkinsonism & related disorders Volume: 18 Suppl 1 Pages: S190-191
  • DOI: 10.1016/S1353-8020(11)70059-1
  • Peer Reviewed
• [Journal Article] Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis (2012)
  • Author(s): Ogaki K, Li Y, Atsuta N, Tomiyama H, Funayama M, Watanabe H, Nakamura R, Yoshino H, Yato S, Tamura A, Naito Y, Taniguchi A, Fujita K, Izumi Y, Kaji R, Hattori N, Sobue G
  • Journal Title: Analysis of C9orf72 repeat expansion in 563 Japanese patients with amyotrophic lateral sclerosis Volume: 33 Pages: 2527 e2511-2526
  • DOI: 10.1016/j.neurobiolaging.2012.05.011
  • Peer Reviewed
• [Journal Article] Nuclear factor kappa B expression in patients with sporadic amyotrophic lateral sclerosis and hereditary amyotrophic lateral sclerosis with optineurin mutations (2012)
  • Author(s): Sako W, Ito H, Yoshida M, Koizumi H, Kamada M, Fujita K, Hashizume Y, Izumi Y, Kaji R
  • Journal Title: Clinical neuropathology Volume: 31 Pages: 418-423
  • DOI: 10.5414/NP300493
  • Peer Reviewed
• [Journal Article] The TRK-fused gene is mutated in hereditary motor and sensory neuropathy with proximal dominant involvement (2012)
  • Author(s): shiura H, Sako W, Yoshida M, Kawarai T, Tanabe O, Goto J, Takahashi Y, Date H, Mitsui J, Ahsan B, Ichikawa Y, Iwata A, Yoshino H, Izumi Y, Fujita K, Maeda K, Goto S, Koizumi H, Morigaki R, Ikemura M, Yamauchi N, Murayama S, Nicholson GA, Ito H, Sobue G, Nakagawa M, Kaji R, Tsuji S
  • Journal Title: American journal of human genetics Volume: 91 Pages: 320-329
  • DOI: 10.1016/j.ajhg.2012.07.014
  • Peer Reviewed
• [Journal Article] Brainstem and spinal cord motor neuron involvement with optineurin inclusions in proximal-dominant hereditary motor and sensory neuropathy (2011)
  • Author(s): Fujita K, Yoshida M, Sako W, Maeda K, Hashizume Y, Goto S, Sobue G, Izumi Y, Kaji R
  • Journal Title: J Neurol Neurosurg Psychiatry Volume: 83 Pages: 1402-3
  • DOI: 10.1136/jnnp-2011-300783
  • Peer Reviewed
• [Journal Article] Can Awaji ALS criteria provide earlier diagnosis than the revised El Escorial criteria? (2011)
  • Author(s): Okita T1, Nodera H, Shibuta Y, Nodera A, Asanuma K, Shimatani Y, Sato K, Izumi Y, Kaji R
  • Journal Title: J Neurol Sci Volume: 302 Pages: 29-32
  • DOI: 10.1016/j-jns.2010.12.007
  • Peer Reviewed
• [Presentation] TFG 変異による運動ニューロン死のメカニズム (2013)
  • Author(s): 梶 龍兒、森田光哉、瓦井俊孝、森垣龍馬、藤田浩司、野寺裕之、和泉唯信、後藤 惠、中野今治
  • Organizer: 第54回日本神経学会学術大会2013
  • Place of Presentation: 東京国際フォーラム(東京都)
  • Year and Date: 2013-05-31
• [Presentation] Electrophysiological diagnosis of ALS (2011)
  • Author(s): Kaji R
  • Organizer: World Congress of Neurology
  • Place of Presentation: Mansour Eddhabi Congress Center (Marrakesh Morocco)
  • Year and Date: 2011-11-13
• [Book] 神経内科 (2013)
  • Author(s): 瓦井俊孝、森垣龍馬、藤田浩司、和泉唯信、梶 龍兒
  • Total Pages: 766 (751-756)
  • Publisher: 科学評論社
• [Book] 神経内科 (2013)
  • Author(s): 藤田浩司、瓦井俊孝、和泉唯信、後藤 惠、梶 龍兒
  • Total Pages: 766 (732-737)
  • Publisher: 科学評論社
• [Patent(Industrial Property Rights)] THE METHOD OF TREATING AMYOTROPHIC LATERAL SCLEROSIS (2012)
  • Inventor(s): 梶 龍兒
  • Industrial Property Rights Holder: 徳島大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: PCT-JP2012-056217
  • Filing Date: 2012-03-06
  • Overseas