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Nucleic Acid Ther. 2016 Feb;26(1):10-9. doi: 10.1089/nat.2015.0567. Epub 2015 Nov 18.

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

Author information

1
1 Otsuka Pharmaceutical Co., Ltd. , Tokushima, Japan .
2
2 Shin Nippon Biomedical Laboratories, Ltd. , Drug Safety Research Laboratories, Kagoshima, Japan .
3
3 SomaLogic, Inc. , Boulder, Colorado.

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.

PMID:
26579954
PMCID:
PMC4753578
DOI:
10.1089/nat.2015.0567
[Indexed for MEDLINE]
Free PMC Article

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