Study on pathomechanisms of canine degenerative myelopathy and preclinical trial for antibody therapy

• Project/Area Number: 24380169
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical veterinary science
• Research Institution: Gifu University
• Principal Investigator: KAMISHINA Hiroaki 岐阜大学, 応用生物科学部, 准教授 (50506847)
• Co-Investigator(Kenkyū-buntansha): MAEDA Sadatoshi 岐阜大学, 応用生物科学部, 教授 (50377694) ; URUSHITANI Makoto 京都大学, 医学部, 准教授 (60332326) ; KATO Shinsuke 鳥取大学, 医学部, 准教授 (60194817)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000); Fiscal Year 2012: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 神経変性疾患 / 変性性脊髄症 / 犬 / 抗体療法 / ミクログリア / ミスフォールド / 神経変性 / ALS

Outline of Final Research Achievements

This research was conducted to elucidate pathomechanisms of canine degenerative myelopathy and develop a novel antibody therapy for this disease. Immunohistochemistry of spinal cord of affected dogs revealed accumulation of activated microglia in the early phase of the degenerating region. Microglia seemed to produce cytotoxic mediators; therefore inhibition of activated microglia was thought to be a promising therapeutic strategy. In this research, we generated canine mutant SOD1-specific antibodies. We are currently working to develop a novel antibody-based therapy for DM using our canine mutant SOD1-specific antibodies.

Research Products

• [Journal Article] Genotyping Assays for the Canine Degenerative Myelopathy-Associated c,118G>A (p.E40K) Mutation of the SOD1 Gene Using Conventional and Real-Time PCR Methods : A High Prevalence in the Pembroke Welsh Corgi Breed in Japan. (2013)
  • Author(s): Chang H.S., Kamishina H., Mizukami K., Momoi Y., Katayama M., Rahman M.M., Uddin M.M., Yabuki A., Kohyama M., Yamato O.
  • Journal Title: Journal of Veterinary Medical Science Volume: (in press)
  • NAID: 120006342278
  • Peer Reviewed
• [Presentation] Clinical, histopathological, and biochemical characterization of the canine model of SOD1-mediated amyotrophic lateral sclerosis (2014)
  • Author(s): Kobatake Yui, Oyake Kanae, Tsukui Toshihiro, Sakai Hiroki, Yamato Osamu, Saito Miyoko, Urushitani Makoto, Kato Shinsuke, Sasaki Jun, Shibata Sanae, Maeda Sadatoshi, Kamishina Hiroaki
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-13
• [Presentation] イヌ変性性脊髄症に認められる変異型SOD1蛋白（E40K）に対する モノクローナル抗体の作製と特異性の解析 (2013)
  • Author(s): 小畠結, 漆谷真, 加藤信介, 酒井洋樹, 大和修, 津久井利広, 鈴木理恵子, 前田貞俊, 神志那弘明
  • Organizer: 第156回日本獣医学会学術集会
  • Place of Presentation: 岐阜
• [Presentation] イヌの変性性脊髄症における変異型SOD1蛋白凝集体の証明 (2012)
  • Author(s): 中前早百合, 漆谷真, 加藤信介, 酒井洋樹, 大和修, 内田和幸, 小川瑞恵, 津久井利広, 鈴木理恵子, 前田貞俊, 神志那弘明
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
  • Year and Date: 2012-09-16
• [Presentation] イヌの変性性脊髄症におけるミクロクリアの組織学的解析と細胞傷害因子の定量 (2012)
  • Author(s): 山田修平, 酒井洋樹, 千村直輝, 漆谷真, 大和修, 加藤信介, 内田和幸, 小川瑞恵, 前田貞俊, 神志那弘明
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
  • Year and Date: 2012-09-16
• [Presentation] イヌの変性性脊髄症に認められる変異型SOD1蛋白の生化学的解析 (2012)
  • Author(s): 並木まり子, 漆谷真, 大和修, 津久井利広, 鈴木理恵子, 加藤信介, Janice Robertson, Kate Banks, 前田貞俊, 神志那弘明
  • Organizer: 第154回日本獣医学会学術集会
  • Place of Presentation: 岩手大学(盛岡市)
  • Year and Date: 2012-09-16