VEGF Inhibition as a Therapeutic for Airway Inflammatory Disorders such as CRSwNP

UNMET NEED: A hallmark of chronic rhinosinusitis (CRS) with hyperplastic sinonasal polyposis (CRSwNP), one of the most severe forms of CRS, is the mucosal hyperplasia, resulting in chronic disease that becomes refractory to either medical or surgical management. Histological features of CRSwNP resemble that of asthmatic airways; yet, despite the significant morbidity of recurrent disease, central mechanisms regarding the pathogenesis of sinonasal polyposis remain poorly understood. Here, inventors demonstrate that VEGF (vascular endothelial cell growth factor) is a central pathway by which airway epithelial cell growth is regulated and suggest methods of inhibiting VEGF-A, and/or VEGFR1, and/or VEGFR2, and/or NP1 (neurophilin-1) as therapeutic strategies to treat CRSwNP, as well as asthma. Advantages include:

• Inhibition of growth factor promotes blockage of epithelial cell proliferation therefore preventing the formation of sinonasal polyps associated with CRSwNP.
• Inhibition of growth factor promotes apoptosis of epithelial cells resulting in a reduction of sinonasal polyps associated with CRSwNP.

 
TECHNICAL DETAILS: One of the most prominent features contributing to the morbidity of CRSwNP patients, despite treatment with glucocorticoids, is exuberant re-growth of diseased sinus mucosa necessitating repeated surgical intervention. Using in vivo and in vitro human experimental models JHU scientists have demonstrated overexpression of VEGF in the nasal tissues of patients with CRSwNP. Administration of inhibitors of expression and/or activity of VEGF, NP-1, VEGFR1, VEGFR2, or combinations thereof, was shown to block epithelial cell growth and promotes apoptosis. This presents a promising new strategy to treat a variety of airway inflammatory disorders, for which dysfunctional airway epithelial cells are central, including CRSwNP, chronic rhinosinusitis without nasal polyposis, asthma, COPD, allergic and/or nonallergic rhinitis, or allergic bronchopulmonary aspergillosis, or cystic fibrosis.
 
INVENTORS: Jean Kim
 
 PATENT STATUS: Granted US Patent 9,289,475

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