Complete remission induction therapy development of multiple sclerosis by selective - timed activation of the protective microglia

• Project/Area Number: 25461282
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Kyushu University
• Principal Investigator: Yamasaki Ryo 九州大学, 大学病院, 講師 (10467946)
• Co-Investigator(Kenkyū-buntansha): MASAKI Katsuhisa 九州大学, 大学院医学研究院, 助教 (90612903) ; 河野 祐治 九州大学, 医学(系)研究科(研究院), 研究員 (20333479)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2014: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: ミクログリア / 多発性硬化症 / アストログリア / 実験的自己免疫性脳脊髄炎 / 筋萎縮性側索硬化症 / EDNRB / エンドセリン / 単球 / マクロファージ

Outline of Final Research Achievements

Whether microglia which activated in the spinal cord lesions of multiple sclerosis model mice are neuroprotective or neurotoxic is controversial. We have reviewed the gene expression pattern of microglia and discovered that these activated microglia expressed neuroprotective factors. In this study, we aimed to develop new treatment for the chronic phase of multiple sclerosis which there are currently no treatment options by amplifying neuroprotective effect of microglia. In the previous gene expression analysis, expression of EDNRB was up-regulated in activated microglia. It was able to reduce the severity of the disease by the administration of the selective antagonist of EDNRB, BQ788. Therefore, BQ788 was expected as a new therapeutic agents to treat chronic phase of multiple sclerosis.

Research Products

• [Journal Article] Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model. (2014)
  • Author(s): Cui Y and Masaki K et al
  • Journal Title: J Neuroinflammation Volume: 11 Issue: 1 Pages: 42-42
  • DOI: 10.1186/1742-2094-11-42
  • Peer Reviewed / Open Access
• [Journal Article] Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica. (2013)
  • Author(s): Masaki K, Suzuki SO, Matsushita T, Matsuoka T, Imamura S, Yamasaki R, Suzuki M, Suenaga T, Iwaki T, Kira J.
  • Journal Title: PLoS One. Volume: 8
  • Peer Reviewed
• [Journal Article] Anti-neurofascin antibody in patients with combined central and peripheral demyelination (2013)
  • Author(s): Nobutoshi Kawamura, Ryo Yamasaki, Tomomi Yonekawa, Takuya Matsushita, Susumu Kusunoki, Shigemi Nagayama, Yasuo Fukuda, Hidenori Ogata, Dai Matsuse, Hiroyuki Murai, Jun-ichi Kira
  • Journal Title: Neurology Volume: 81 Issue: 8 Pages: 714-722
  • DOI: 10.1212/wnl.0b013e3182a1aa9c
  • Peer Reviewed
• [Journal Article] TAR DNA-binding protein 43 pathology in a case clinically diagnosed with facial-onset sensory and motor neuronopathy syndrome: an autopsied case report and a review of the literature. (2013)
  • Author(s): Sonoda K, Sasaki K, Tateishi T, Yamasaki R, Hayashi S, Sakae N, Ohyagi Y, Iwaki T, Kira J.
  • Journal Title: J Neurol Sci Volume: 332 Issue: 1-2 Pages: 148-153
  • DOI: 10.1016/j.jns.2013.06.027
  • Peer Reviewed
• [Journal Article] A case of hereditary diffuse leukoencephalopathy with axonal spheroids caused by a de novo mutation in CSF1R masquerading as primary progressive multiple sclerosis. (2013)
  • Author(s): Saitoh BY, Yamasaki R, Hayashi S, Yoshimura S, Tateishi T, Ohyagi Y, Murai H, Iwaki T, Yoshida K, Kira J.
  • Journal Title: Mult Scler. Volume: 10 Issue: 10 Pages: 1367-1370
  • DOI: 10.1177/1352458513489854
  • Peer Reviewed
• [Presentation] Atopic disease model mice express more severe signs at the chronic phase of EAE. (2016)
  • Author(s): 山崎 亮
  • Organizer: 第57回日本神経学会
  • Place of Presentation: 神戸コンベンションセンター
  • Year and Date: 2016-05-19
• [Presentation] 炎症性脱髄病巣におけるミクログリアの役割
  • Author(s): 山崎 亮
  • Organizer: 第55回日本神経学会総会
  • Place of Presentation: 福岡国際会議場
  • Invited