Chemically Modified Interleukin-6 Aptamer Inhibits Development of Collagen-Induced Arthritis in Cynomolgus Monkeys

Masao Hirota, Ikuo Murakami, Yuichi Ishikawa, Tomoki Suzuki, Shun Ichiro Sumida, Shigeru Ibaragi, Hayato Kasai, Naoto Horai, Daniel W. Drolet, Shashi Gupta, Nebojsa Janjic, Daniel J. Schneider

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16 Citations (Scopus)

Abstract

Interleukin-6 (IL-6) is a potent mediator of inflammatory and immune responses, and a validated target for therapeutic intervention of inflammatory diseases. Previous studies have shown that SL1026, a slow off-rate modified aptamer (SOMAmer) antagonist of IL-6, neutralizes IL-6 signaling in vitro. In the present study, we show that SL1026 delays the onset and reduces the severity of rheumatoid symptoms in a collagen-induced arthritis model in cynomolgus monkeys. SL1026 (1 and 10 mg/kg), administered q.i.d., delayed the progression of arthritis and the concomitant increase in serum IL-6 levels compared to the untreated control group. Furthermore, SL1026 inhibited IL-6-induced STAT3 phosphorylation ex vivo in T lymphocytes from human blood and IL-6-induced C-reactive protein and serum amyloid A production in human primary hepatocytes. Importantly, SOMAmer treatment did not elicit an immune response, as evidenced by the absence of anti-SOMAmer antibodies in plasma of treated monkeys. These results demonstrate that SOMAmer antagonists of IL-6 may be attractive agents for the treatment of IL-6-mediated diseases, including rheumatoid arthritis.

Original languageEnglish
Pages (from-to)10-19
Number of pages10
JournalNucleic Acid Therapeutics
Volume26
Issue number1
DOIs
Publication statusPublished - Feb 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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  • Cite this

    Hirota, M., Murakami, I., Ishikawa, Y., Suzuki, T., Sumida, S. I., Ibaragi, S., Kasai, H., Horai, N., Drolet, D. W., Gupta, S., Janjic, N., & Schneider, D. J. (2016). Chemically Modified Interleukin-6 Aptamer Inhibits Development of Collagen-Induced Arthritis in Cynomolgus Monkeys. Nucleic Acid Therapeutics, 26(1), 10-19. https://doi.org/10.1089/nat.2015.0567