Further confirmation of the therapeutic potential of Toll Like Receptor 9 (TLR9) antagonists on type 2 airway Inflammation: allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP)

Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) share a type 2 inflammatory pathway underlying chronicity and burden of disease, with potential progress to asthma. Our Leuven data show that 40% of AR and CRSwNP patients remain uncontrolled despite guideline-based treatment, with major impact on quality of life and health economy. This shared immune pathway therefore needs to be addressed by novel treatments. Together with IVAP, we have obtained pre-clinical unpublished data indicating that newly designed Toll-like receptor (TLR)-9 antagonists are able to inhibit type 2 inflammation in nasal explants of CRSwNP patients and in mice with house dust mite-induced allergic inflammation. We aim to further explore the therapeutic potential of these antagonists on type 2 airway inflammation using different in vitro and in vivo models. Therefore, our consortium of research experts in the field of clinical immunology, medicinal chemistry and structural biology will be continued. This collective effort will drive hit-to-lead optimization and may lead to a new treatment strategy for type 2 inflammatory airway diseases.

Keywords:TLR9 Antagonists, Allergic Rhinitis, Chronic Rhinosinusitis with Nasal Polyps, Type 2 inflammation, Epithelial barrier

Disciplines:Applied immunology