Idera Pharmaceuticals, Inc. (Nasdaq: IDRA), a clinical stage biopharmaceutical company developing a novel therapeutic approach for the treatment of autoimmune diseases and genetically defined forms of B-cell lymphoma, today announced the publication of a study supporting the potential role of the suppression of Toll-like-receptors (TLRs) 7, 8, and 9 in the treatment of psoriasis. The data were published in the scientific journal PLOS ONE.
In the publication, entitled Suppression of Molecular Inflammatory Pathways by Toll-Like Receptor 7, 8, and 9 Antagonists in a Model of IL-23-Induced Skin Inflammation, data are presented from a study of an antagonist of TLRs 7 and 9 and an antagonist of TLRs 7, 8, and 9. The IL-23-induced mouse model of skin inflammation was chosen due to its histological and molecular resemblance to human psoriasis, including the involvement of the IL-17 inflammatory pathway. Gene expression analyses showed that treatment with either antagonist normalized expression of IL-17-induced genes. Additionally, both antagonists normalized aberrant expression of keratin 16, an indicator of epidermal hyperplasia. More of the IL-23 regulated genes were modulated with the antagonist of TLRs 7, 8, and 9 (36%) than with the antagonist of TLRs 7, and 9 (26%). In addition to IL-17, other inflammatory pathways, including IL-6 and interferon-gamma, were strongly suppressed by both antagonists. Further analysis showed that the antagonist of TLRs 7, 8, and 9 down-regulated the JAK-STAT, IL-23, IL-12, and IL-17 canonical pathways. The results suggest that IL-23-driven inflammation in mouse skin may be dependent on signaling mediated by TLRs 7, 8, and 9.
“These results indicate that TLRs 7, 8 and 9 could serve as novel therapeutic targets in psoriasis vulgaris and other disease with similar pathophysiology,” stated James G. Krueger, M.D., Ph.D., Head of the Laboratory for Investigative Dermatology at The Rockefeller University and senior study author.
“These data provide further insight into the mechanisms underlying the therapeutic effect which we have reported previously in our TLR antagonist clinical program in psoriasis. Currently, we are conducting a Phase 2 clinical trial of IMO-8400, an antagonist of TLRs 7, 8, and 9, for the treatment of patients with moderate-to-severe plaque psoriasis and plan to initiate clinical development in selected orphan autoimmune indications,” said Robert D. Arbeit, M.D., Vice President of Clinical Development at Idera.