The efficancy of calcium release-activated calcium channel inhitibors in the treatment of rheumatoid arthritis

• Project/Area Number: 15K19575
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Ehime University
• Principal Investigator: Liu Shuang 愛媛大学, 医学系研究科, 講師 (60403812)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: カルシウムチャネル阻害剤 / 免疫抑制剤 / 関節リウマチ / 抗体製剤 / 核酸製剤 / Short-hairpin RNA / CARCチャネル阻害薬 / ヒト型関節リウマチモデル / SCIDマウス / 薬理効果 / 臨床研究

Outline of Final Research Achievements

In this study, the inhibitors of calcium release-activated calcium channel (CRAC), including small molecular compound YM-58483, neutralizing antibody, and shor-harpin RNA, were used to investigate the feasibility in the treatment of rheumatoid arthritis (RA). The efficacy of CRAC inhibitors was demonstrated according to the results of this study. The CRAC inhibitors are expected as a group of new globle immunosuppressants.

Research Products

• [Journal Article] Efficacy of constant long-term delivery of YM-58483 for the treatment of rheumatoid arthritis (2018)
  • Author(s): Miyoshi Maya、Liu Shuang、Morizane Asuka、Takemasa Erika、Suzuki Yashuyuki、Kiyoi Takeshi、Maeyama Kazutaka、Mogi Masaki
  • Journal Title: Eur J Pharmacol. Volume: 824 Pages: 89-98
  • DOI: 10.1016/j.ejphar.2018.02.006
  • Peer Reviewed
• [Journal Article] Zoledronate modulates intracellular vesicle trafficking in mast cells via disturbing the interaction of myosinVa/Rab3a and sytaxin4/VAMP7 (2018)
  • Author(s): Liu Shuang、Sahid Muhammad N.A.、Takemasa Erika、Maeyama Kazutaka、Mogi Masaki
  • Journal Title: Biochem Pharmacol. Volume: 151 Pages: 18-25
  • DOI: 10.1016/j.bcp.2018.02.013
  • Peer Reviewed
• [Journal Article] Functional G-Protein-Coupled Receptor (GPCR) Synthesis: The Pharmacological Analysis of Human Histamine H1 Receptor (HRH1) Synthesized by a Wheat Germ Cell-Free Protein Synthesis System Combined with Asolectin Glycerosomes (2018)
  • Author(s): Suzuki Yasuyuki、Ogasawara Tomio、Tanaka Yuki、Takeda Hiroyuki、Sawasaki Tatsuya、Mogi Masaki、Liu Shuang、Maeyama Kazutaka
  • Journal Title: Frontiers in Pharmacology Volume: 9 Pages: 38-38
  • DOI: 10.3389/fphar.2018.00038
  • Peer Reviewed / Open Access
• [Journal Article] Efficiency and Safety of CRAC Inhibitors in Human Rheumatoid Arthritis Xenograft Models (2017)
  • Author(s): Liu Shuang、Hasegawa Hitoshi、Takemasa Erika、Suzuki Yasuyuki、Oka Keizou、Kiyoi Takeshi、Takeda Hiroyuki、Ogasawara Tomio、Sawasaki Tatsuya、Yasukawa Masaki、Maeyama Kazutaka
  • Journal Title: The Journal of Immunology Volume: 199 Issue: 5 Pages: 1584-1595
  • DOI: 10.4049/jimmunol.1700192
  • Peer Reviewed / Open Access
• [Journal Article] Intra-articular lentivirus-mediated gene therapy targeting CRACM1 for the treatment of collagen-induced arthritis (2017)
  • Author(s): Shuang Liu, Takeshi Kiyoi, Erika Takemasa, Kazutaka Meayama
  • Journal Title: Journal of Pharmacological Sciences Volume: 133 Issue: 3 Pages: 130-138
  • DOI: 10.1016/j.jphs.2017.02.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] CRAC3 regulates the stability of non-excitable vesicle fusion pores in a Ca2+-independent manner via molecular interaction with syntaxin4 (2016)
  • Author(s): Liu S, Sahid MNA, Takemasa E, Kiyoi T, Kuno M, Oshima Y and Maeyama K
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 1-14
  • DOI: 10.1038/srep28133
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Gene Therapy for Rheumatoid Arthritis (2016)
  • Author(s): Liu S, Maeyama K
  • Journal Title: Crit Rev. Immunol. 2016;36(2):149-161. Volume: 36 Issue: 2 Pages: 149-161
  • DOI: 10.1615/critrevimmunol.2016017062
  • Peer Reviewed
• [Journal Article] Systemic Lentivirus-Mediated Delivery of Short Hairpin RNA Targeting Calcium Release-Activated Caclium Channel 3 as Gnen Therapy for Collagen-Induced Arthritis (2015)
  • Author(s): Shuang Liu, Takeshi Kiyoi, Erika Takemasa, Kazutaka Meayama
  • Journal Title: The Journal of Immunology Volume: 194 Issue: 1 Pages: 76-83
  • DOI: 10.4049/jimmunol.1401976
  • Peer Reviewed
• [Presentation] Intra-articular treatment of short hairpin RNA targeting calcium release-activated calcium channel 1 in collagen-induced arthritis mice (2017)
  • Author(s): 劉爽、清井武志、前山一隆
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎
  • Year and Date: 2017-03-15
• [Presentation] The inhibition of store-operated Ca2+ entry through calcium release-activated calcium channel in the treatment of rheumatoid arthritis (2017)
  • Author(s): 劉爽、長谷川均、清井武志、前山一隆
  • Organizer: 第90回日本薬理学会年会
• [Presentation] The efficiency of the regulation of Ca2+ entry through calcium release-activated calcium channel in the treatment of rheumatoid arthritis (2016)
  • Author(s): Shuang Liu、Erika Takemasa、Takeshi Kiyoi, Maeyama Kazutaka
  • Organizer: American College of Rheumatology Annual Meeting2016
  • Place of Presentation: Washingtpn D.C.
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] YM-58483の有効な投与方法と関節炎治療効果の検討 (2016)
  • Author(s): 三好真綾、森実あすか、劉爽、前山一隆
  • Organizer: 日本薬学会第136年会
  • Place of Presentation: パシフィッコ横浜(神奈川県横浜市）
  • Year and Date: 2016-03-26
• [Presentation] Intra-articular treatment of Short Hairpin RNA Targeting Calcium Release-Activated Calcium channel 1 in Collagen-Induced Arthritis mice. (2016)
  • Author(s): Shuang Liu、Erika Takemasa、Takeshi Kiyoi, Maeyama Kazutaka
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィッコ横浜(神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] The therapeutic effect of YM-58483 on collagen-induced arthritis mice (2016)
  • Author(s): Asuka Morizane, Maya Miyoshi, Shuang Liu, Maeyama Kazutaka
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィッコ横浜(神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] Chracterization of receptors responsible for basic compound-activation on mast cells: focus on as-related B protein-coupled receptors (2016)
  • Author(s): Muhammad Novrizal Abdi Sahid, Shuang Liu, Takeshi Kiyoi, Kazutaka Maeyama
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィッコ横浜(神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] Histamine Uptake Mechanism i mast cells via uptake-2 system transporters: investigation using rat basophilic leukemia subclone (RBL-2H3 Sc98) cells (2016)
  • Author(s): Trivadila Trivadila, Muhammad Novrizal Abdi Sahid, Shuang Liu, Kazutaka Maeyama
  • Organizer: 第89回日本薬理学会年会
  • Place of Presentation: パシフィッコ横浜(神奈川県横浜市）
  • Year and Date: 2016-03-09
• [Presentation] コラーゲン誘発関節炎モデルマウスにおけるYM-58483による治療効果の検討 (2015)
  • Author(s): 三好真綾、森実あすか、劉爽、前山一隆
  • Organizer: 第68回日本薬理学会西南部会
  • Place of Presentation: 海峡メッセ下関（山口県下関市）
  • Year and Date: 2015-11-21