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GLP-1 Hormone in Severe Asthma

Institution: University of California, Davis
Investigator(s): Nicholas Kenyon, M.D.,M.A.
Award Cycle: 2019 (Cycle 28) Grant #: 28IR-0051 Award: $937,500
Subject Area: Pulmonary Disease
Award Type: High Impact Research Project Award

Initial Award Abstract

Tobacco smoke leads to worsening of asthma symptoms, and this is particularly true in non-allergic asthmatics. Non-allergic asthma in adulthood and obesity appear to be linked, but the mechanisms underlying this are not well understood. We have shown that high insulin levels inhibit the function of a receptor molecule on human airway cells, and this may impair the effectiveness of inhaler medications. We have data that suggests this can be overcome by the addition of the drug roflumilast and the hormone glucagon-like peptide 1 (GLP-1, e.g. mimicked by liraglutide). Studying GLP-1/liraglutide and drugs like roflumilast allows us to examine a mechanism potentially linking obesity and asthma and identify readily available and safe therapeutic options to treat a subgroup of asthmatics that are particularly prone to the adverse effects of tobacco smoke. We hypothesize that high insulin levels contribute to asthma by impairing function of the receptor molecule on airway cells and that this can be rescued by GLP-1 and roflumilast and we will test our hypothesis in cell culture studies, animal studies using a combined obesity and asthma model, and in a clinical trial testing whether liraglutide and roflumilast can improve response to asthma medications.