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Prostaglandin D2 type 2 receptor antagonism reduces airway smooth muscle mass in asthma: mechanistic insights from in vitro and computational models

Saunders, Ruth and Kaul, Himanshu and Berair, Rachid and Gonem, Sherif and Singapuri, Amisha and Sutcliffe, Amanda and Latifa, Chachi and Biddle, Michael and Kaur, Davinder and Bourne, Michelle and Pavord, Ian and Wardlaw, Andrew and Siddiqui, Salman and Brook, Bindi and 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

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