A clinical trial studying the use of Verapamil (a drug currently in use for cardiovascular disease (CVD) and cluster headache) in alleviating chronic rhinosinusitis (CRS) with nasal polyps revealed significant improvement in the symptoms of this subset of patients.
It is the first study of its kind to explore treatment for CRS by inhibiting P-glycoprotein, a protein pump within the nasal lining that Massachusetts Eye and Ear researchers previously identified as a mechanism for these severe cases of CRS marked by the presence of nasal polyps. The clinical trial results suggest that Verapamil represents a promising novel therapy for the treatment of CRS with nasal polyps.
"Recently, we became aware that some of the inflammation in CRS with nasal polyps is generated by the nasal lining itself, when a particular protein pump (P-glycoprotein) is overexpressed and leads to the hyper-secretion of inflammatory cytokines," said senior author Dr Benjamin S Bleier, a sinus surgeon at Mass. Eye and Ear and an assistant professor of otolaryngology at Harvard Medical School. "Verapamil is a first-generation inhibitor that is well-established in blocking P-glycoprotein. In some patients with CRS with nasal polyps, we saw dramatic improvement in their symptom scores."
One of the more prevalent chronic illnesses in the US, CRS has been known to cause significant quality of life detriments to affected patients, who often cannot breathe or sleep easily due to obstructed nasal and sinus passages. The presence of nasal polyps represents a particularly severe presentation of the disease. Current treatment strategies (most often long-term steroid use) are plagued by difficult side effects and fail to target an underlying source of the disease.
Motivated by their previous finding of the presence of P-glycoprotein over-expression in the nasal lining of patients with CRS with nasal polyps, the study authors conducted a randomized, double-blind, placebo-controlled clinical trial studying the use of low-dose Verapamil in 18 patients with CRS with nasal polyps. An analysis of these patients demonstrated improved outcomes for those in the Verapamil group in relation to those in the placebo group.
However, the researchers also observed that the treatment effect was significantly limited among patients with higher body mass indices. Future studies are being planned to determine if a higher dose of Verapamil may be needed to be therapeutic for some patients.
"Chronic rhinosinusitis with nasal polyps is among our most challenging diagnoses to treat, because these patients essentially have chronic, lifelong inflammation that needs chronic, lifelong treatment," said Bleier. "We observed no significant side effects at the doses we used, and we are very encouraged by the results of this first step toward a more targeted therapy for our patients."
Abstract
Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by polypoid mucosa and predominantly TH2 inflammation. Epithelial P-glycoprotein (P-gp) is a membrane efflux pump that is overexpressed in CRSwNP1,2 and regulates the secretion of TH2-polarizing cytokines.3 These findings suggest that P-gp may represent a novel druggable target. Verapamil hydrochloride (HCl) is a first-generation inhibitor of P-gp and is capable of blocking IL-5, IL-6, and thymic stromal lymphopoietin secretion.4 Although verapamil is cardioactive, low doses are tolerated by healthy patients with cluster headache.
Authors
Marcel M Miyake, Angela Nocera, Patricia Levesque, Rong Guo, Christine A Finn, Jeremy Goldfarb, Stacey Gray, Eric Holbrook, Nicolas Busaba, Jose Eduardo L Dolci, Benjamin S Bleier
[link url="https://www.sciencedaily.com/releases/2017/01/170123093954.htm"]Massachusetts Eye and Ear material[/link]
[link url="http://www.jacionline.org/article/S0091-6749(16)31444-0/abstract"]Journal of Allergy and Clinical Immunology abstract[/link]