Space Activation for Josh Levy Lab

National Institute On Deafness And Other Communication Disorders

Investigators

Abstract

Our basic science studies are focused on the sinonasal epithelium as a model system to understand chronic inflammatory pathways that are disrupted in sinus disease and other forms of acquired smell/taste loss. We previously discovered an increased expression of the type-2 cannabinoid receptor in Aspirin-exacerbated respiratory disease (AERD), a recalcitrant form of chronic sinusitis with associated loss of smell. This year we have begun to evaluate the physiologic effects of this over-expression in epithelial models from patients with AERD, with a focus on the sinonasal epithelial barrier. Additionally, we have completed a bulk RNA-Seq experiment with comparison of epithelial gene expression among patients with AERD, allergic fungal rhinosinusitis (AFRS) and normal controls without sinus disease or other forms of olfactory dysfunction. AFRS is an equally difficult to treat form of sinus disease with associated loss of smell. Our data reveal novel insights suggesting the role of arachidonic acid and the eicosanoid system in the pathogenesis of both forms of sinus disease. Our translational studies consist of preclinical experiments aimed at developing therapies to reverse chronic epithelial inflammation in humans with loss of smell/taste. Targets of these studies include the eicosanoid and endogenous cannabinoid systems identified as being dysregulated in chronic sinus disease. Clinically we are evaluating the use of dupilumab for the treatment of AFRS and loss of smell. Dupilumab is a respiratory biologic that significantly improves the sense of smell in patients with nasal polyps. However, the efficacy of this intervention among patients with AFRS is yet to be demonstrated in phase III clinical trials. We therefore seek to establish the safety and efficacy in this patient population while collecting patient samples for further study of the mechanisms underlying the impressive impact of this drug on the sense of smell.