Saunders, Ruth, Kaul, Himanshu, Berair, Rachid, Gonem, Sherif, Singapuri, Amisha, Sutcliffe, Amanda, Latifa, Chachi, Biddle, Michael, Kaur, Davinder, Bourne, Michelle, Pavord, Ian, Wardlaw, Andrew, Siddiqui, Salman, Brook, Bindi, Smallwood, Rod and Brightling, Christopher (2019) Prostaglandin D2 type 2 receptor antagonism reduces airway smooth muscle mass in asthma: mechanistic insights from in vitro and computational models. Science Translational Medicine, 11 (479). ISSN 1946-62341946-6242

Abstract

Increased airway smooth muscle mass, a feature of airway remodeling in asthma, is the strongest predictor of airflow limitation, and contributes significantly to asthma-associated morbidity and mortality. No current drug therapy for asthma affects airway smooth muscle mass. We report that the prostaglandin D2 type 2 receptor antagonist, fevipiprant, is the first drug in a randomized placebo-controlled trial to reduce airway smooth muscle mass in asthma. By integrating in vitro experiments with a novel agent-based computational modeling strategy we found this reduction in airway smooth muscle mass was a consequence of inhibiting eosinophilic inflammation in concert with reduced recruitment of myofibroblasts to the airway smooth muscle bundle. Thus, fevipiprant represents a novel therapy to ameliorate airway remodeling in asthma.

Item Type:	Article
Date Deposited:	23 Mar 2019 00:45
Last Modified:	23 Mar 2019 00:45
URI:	https://oak.novartis.com/id/eprint/36523