Trials to treat progressive MS

• Project/Area Number: 26461293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka University
• Principal Investigator: Okuno Tatsusada 大阪大学, 医学系研究科, 助教 (00464248)
• Co-Investigator(Kenkyū-buntansha): 中辻 裕司 大阪大学, 医学系研究科, 准教授 (20332744) ; 甲田 亨 大阪大学, 医学部附属病院, 医員 (70626134) ; 多田 智 大阪大学, 微生物病研究所, 招へい研究員 (70626530)
• Co-Investigator(Renkei-kenkyūsha): Hideki Mochizuki 大阪大学, 医学系研究科, 教授 (90230044) ; Atsuhi Kumanogoh 大阪大学, 医学系研究科, 教授 (10294125)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 多発性硬化症 / 筋萎縮性側索硬化症 / Sema3E / 虚血 / 低酸素 / 血流 / 神経変性 / セマフォリン / EAE / 血管 / 実験的自己免疫性脳脊髄炎

Outline of Final Research Achievements

Multiple Sclerosis(MS) and Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by the pathogenesis of which includes ischemia and hypoxia. However, the precise role of hypoxia in neurodegenerative diseases remains unknown. In this study, we administered a synthetic prostacyclin agonist ONO1301, to animal model of ALS (mSOD1G93A mice) to alleviate ischemia and hypoxia in the spinal cord. Prostacyclin agonist successfully suppressed the expression level of HIF1-αin the spinal cords of mSOD1G93A mice, resulting in the significant prevention of neurodegeneration. Our data is the first documented study to suggest that blood flow increasing therapy has a potential to improve neurodegenrative diseases.

Research Products

• [Journal Article] Polarization of M2 macrophages requires Lamtor1 that integrates cytokine and amino-acid signals (2016)
  • Author(s): Kimura T, Nada S, Takegahara N, OkunoT, NojimaS, Kang S, Ito D, Morimoto K, Morimoto K, Hosokawa T, Hayama Y, Mitsui Y, Sakurai N, Sarashina-Kida H, Nishide M, Maeda Y, Takamatsu H, Okuzaki D, Yamada M, Okada M, Kumanogoh A.
  • Journal Title: Nat Commun Volume: 7 Pages: 13130-13130
  • DOI: 10.1038/ncomms13130
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] LRRK1 is critical in the regulation of B-cell responses and CARMA1-dependent NF-κB activation. (2016)
  • Author(s): Morimoto K, Baba Y, Shinohara H, Kang S, Nojima S, Kimura T, Ito D, Yoshida Y, Maeda Y, Sarashina-Kida H, Nishide M, Hosokawa T, Kato Y, Hayama Y, Kinehara Y, Okuno T, Takamatsu H, Hirano T, Shima Y, Narazaki M, Kurosaki T, Toyofuku T, Kumanogoh A.
  • Journal Title: Sci. Rep. Volume: 6 Pages: 25738-25738
  • DOI: 10.1038/srep25738
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] The role of gut microbiota and diet in EAE and MS (2015)
  • Author(s): 奥野、木下、中辻、望月
  • Journal Title: Clinical & Experimental Neuroimmunology Volume: 6 Pages: 30-37
  • DOI: 10.1111/cen3.12270
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] mTOR Complex Signaling through the SEMA4A-Plexin B2 Axis Is Required for Optimal Activation and Differentiation of CD8+ T Cells. (2015)
  • Author(s): Ito D, Nojima S*, Nishide M, Okuno T, Takamatsu H, Kang S, Kimura T, Yoshida Y, Morimoto K, Maeda Y, Hosokawa T, Toyofuku T, Ohshima J, Kamimura D, Yamamoto M, Murakami M, Morii E, Rakugi H, Isaka Y, Kumanogoh A*. (* correspondence)
  • Journal Title: J Immunol Volume: 195 Pages: 934-43
  • DOI: 10.4049/jimmunol.1403038
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Dietary Yeasts Reduce Inflammation in Central Nerve System via Microflora (2015)
  • Author(s): Takata K, Tomita T, Okuno T, Kinoshita M, Koda T, Honorat JA, Takei M, Hagihara K, Sugimoto T, Mochizuki H, Sakoda S, Nakatsuji Y
  • Journal Title: Annals of Clinical and Translational Neurology Volume: ２ Pages: 55-56
  • DOI: 10.1002/acn3.153
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 11C-Acetate PET Imaging in Patients with Multiple Sclerosis. (2014)
  • Author(s): Takata K, Kato H, Shimosegawa E, Okuno T, Koda T, Sugimoto T, Mochizuki H, Hatazawa J, Nakatsuji Y.
  • Journal Title: PLoSONE Volume: 9
  • DOI: 10.1371/journal.pone.0111598
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Partial suppression of M1microglia by Janus kinase 2 inhibitor does not protect against neurodegeneration in animal models of amyotrophic lateral sclerosi (2014)
  • Author(s): Tada S, Okuno T, Hitoshi Y, Yasui T, Honorat J, Takata K, Koda T, Shimagami H, Chi-Jing C, Namba A,Sugimoto T, Sakoda S, Mochizuki H, Kikutani H, Nakatsuji Y
  • Journal Title: J Neuroinflammation Volume: 11 Pages: 179-179
  • DOI: 10.1186/s12974-014-0179-2
  • Peer Reviewed / Open Access
• [Presentation] 多発性硬化症治療選択バイオマーカーＳｅｍａ４Ａ～フィンゴリモドとの相関について (2016)
  • Author(s): 甲田 亨、奥野 龍禎、中辻 裕司、宮崎雄生、新野正明、深沢俊行、南波明子，山下 和哉、清水幹人、熊ノ郷淳、佐古田三郎、望月 秀樹．
  • Organizer: 第28回 日本神経免疫学会学術集会
  • Place of Presentation: 長崎
  • Year and Date: 2016-09-29
  • Invited
• [Presentation] 多発性硬化症患者における血清Sema4A値高値群の臨床的特徴． (2016)
  • Author(s): 南波 明子，山下 和哉，甲田 亨，奥野 龍禎，熊ノ郷 淳，中辻 裕司，望月 秀樹．
  • Organizer: 57回日本神経学会学術大会
  • Place of Presentation: 神戸
• [Presentation] 多発性硬化症患者における血清Sema4A高値群の臨床的特徴と、IFN-β開始後5年間のNEDA達成率． (2016)
  • Author(s): 南波明子，奥野龍禎，甲田亨，宮崎雄生，新野正明，宮本勝一，楠進，熊ノ郷淳，中辻裕司，望月秀樹
  • Organizer: 第28回日本神経免疫学会学術集会
  • Place of Presentation: 長崎
• [Presentation] NMOsdにおいて血中Sema4Aは増加する (2016)
  • Author(s): 榊原佳織，奥野 龍禎，甲田 亨，宮崎雄生，新野正明，宮本勝一，楠進，深沢俊行，熊ノ郷淳，望月 秀樹 中辻 裕司．
  • Organizer: 第28回 日本神経免疫学会学術集会
  • Place of Presentation: 長崎
• [Presentation] Involvement of Sema4A in multiple sclerosis and neuromyelitis optica. (2014)
  • Author(s): Tatsusada Okuno, Toru Koda, Katsuichi Miyamoto, Kazushiro Takata, Josephe A. Honorat, Susumu Kusunoki, Atsushi Kumanogoh, Yuji Nakatsuji, Hideki Mochizuki.
  • Organizer: The 12th International Congress of Neuroimmunology.
  • Place of Presentation: Ｍainz, Ｇermany
  • Year and Date: 2014-11-09 – 2014-11-13
• [Presentation] 血清Sema4A増加を示すNMO spectrum disordersの臨床的特徴の解析 (2014)
  • Author(s): 奥野龍禎、甲田亨、宮本勝一、中辻裕司、高田和城、オノラ ジョセフ、木下允、楠進、熊ノ郷淳、望月秀樹
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-22
• [Presentation] プロスタグランジンI2 アゴニストであるONO-1301はALSモデル動物の神経変性を抑制する。 (2014)
  • Author(s): 多田智、安居輝人、奥野龍禎、中辻裕司、酒井芳紀、宮川繁、澤芳樹、菊谷仁、佐古田三郎、望月秀樹
  • Organizer: 第55回日本神経学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2014-05-22
• [Book] Neuromyelitis Optica:Diagnosis and Treatment. Neuroimmunological Disease (Kusunoki S). (2016)
  • Author(s): Nakatuji Y, Kinoshita M, Okuno T, Takata K, Koda T, Honorat JA, Sakoda S, Mochizuki H.
  • Publisher: Springer
• [Book] 神経系の慢性炎症 (2014)
  • Author(s): 奥野龍禎 島上洋 望月秀樹
  • Total Pages: 6
  • Publisher: 北隆館