Mucosal healing of IBD by regulation of sugar chain

• Project/Area Number: 15K08966
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Niigata University of Health and Welfare (2016-2018); Niigata University (2015)
• Principal Investigator: Suzuki Kenji 新潟医療福祉大学, 医療経営管理学部, 教授 (00303123)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 炎症性腸疾患 / 線維化 / 粘膜治癒 / 内視鏡 / 糖鎖 / siRNA / CHST15 / コンドロイチン硫酸 / 核酸医薬 / RNA干渉 / コンドロイチン硫酸E

Outline of Final Research Achievements

We have developed a novel si RNA medicine STNMO1 targeting CHST15 which inhibits inflammation and fibrosis in animal colitis model. We have performed Phase I clinical trial of STNM01 for patients with Crohn's disease in Japan. Our newly developed method of endoscopic mucosal injection of STNM01 have shown increased mucosal healing as well as anti-fibrosis effect without any adverse reaction in human as well as in animals. This JSPS funded research has revealed the mechanism of mucosal healing by STNM01, and suggests regulation of sugar chain using STNM01 could be a new treatment option for not only Crohn's disease but also for ulcerative colitis.

Academic Significance and Societal Importance of the Research Achievements

抗TNFα抗体に代表される生物学的製剤により炎症性腸疾患の治療は大いに進歩したが、炎症性腸疾患の難治例では線維化による腸管狭窄や粘膜治癒の遅れのためにこれらの新薬によってもコントロール不良の患者さんが依然存在する。
今回我々が開発した新薬STNM01は糖鎖を制御する核酸医薬siRNAであり、これまでの抗体医薬とは異なったカテゴリーの薬剤であり、線維化による腸管狭窄や粘膜治癒促進効果も期待され、クローン病のみならず潰瘍性大腸炎に対しても新たな治療薬となることが期待される。

Research Products

• [Journal Article] Phase 1 clinical study of siRNA targeting carbohydrate sulphotransferase 15 in Crohn's disease patients with active mcosal lesions. (2017)
  • Author(s): Suzuki K, Yokoyama J, Kawauchi Y, Honda Y, Sato H, Aoyagi Y, Terai S, Okazaki K, Suzuki Y, Sameshima Y, Fukushima T, Sugahara K, Atreya R. Neurath, MF, Watanabe K, Yoneyama H, Asakura H.
  • Journal Title: Jouranal of Crohn's and Colitis Volume: - Pages: 1-8
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis (2016)
  • Author(s): Suzuki K, Arumugam S, Yokoyama J, Kawauchi Y, Honda Y, Sato H, Aoyagi Y, Terai S, Okazaki K, Suzuki Y, Mizumoto S, Sugahara K, Atreya R, Neurath MF, Watanabe K, Hashiguchi T, Yoneyama H, Asakura H: .
  • Journal Title: PloS one Volume: 11 Issue: 7 Pages: 1-17
  • DOI: 10.1371/journal.pone.0158967
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Telmisartan treatment targets inflammatory cytokines to suppress the pathogenesis of acute colitis induced by dextran sulphate sodium. (2015)
  • Author(s): Arumugam S, Sreedhar R, Thandavarayan RA, Giridharan VV, Karuppagounder V, Pitchaimani V, Afrin MR, Miyashita S, Nomoto M, Harima M, Suzuki H, Nakamura T, Nakamura M, Suzuki K, Watanabe K.
  • Journal Title: Cytokine Volume: 15 Issue: 2 Pages: 305-312
  • DOI: 10.1016/j.cyto.2015.03.017
  • Peer Reviewed
• [Journal Article] Small interfering RNA therapy against carbohydrate sulfotransferase 15 inhibits cardiac remodeling in rats with dilated cardiomyopathy. (2015)
  • Author(s): Watanabe K, Arumugam S, Sreedhar R, Thandavarayan RA, Nakamura T, Nakamura M, Harima M, Yoneyama H, Suzuki K.
  • Journal Title: Cell Signal Volume: 15 Issue: 7 Pages: 1517-1524
  • DOI: 10.1016/j.cellsig.2015.03.004
  • Peer Reviewed