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Lookup NU author(s): Dr Polina YarovaORCiD
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Chronic obstructive pulmonary disease (COPD) is predicted to be the third biggest cause of mortality by 2020 (WHO). Unlike asthma, there are no drugs available for COPD that can reduce the progressive decline in lung function. Therefore, there is clearly an unmet need for new therapeutics. Previously, we have shown that calcium-sensing receptor (CaSR) activation elicits airways hyperresponsiveness and inflammation in pre-clinical in vivo mice models of asthma. However, the role of CaSR in the progression of COPD is currently unknown. In the current study, the anti-inflammatory effects of the inhaled negative allosteric CaSR modulator, calcilytic NPS89636, were studied in an in vivo model of COPD induced in guinea pigs by inhalation of lipopolysaccharide (LPS); as in human subjects with COPD, pulmonary inflammation, airways obstruction and remodelling in the guinea pigs have been previously shown to be insensitive to inhaled corticosteroids. Here, we show that treatment with NPS89636 reduced airways inflammation, specifically blood leukocyte and neutrophil infiltration, in airways of LPS-treated animals. In addition, calcilytic treatment reduced lung interstitial wall thickening. These effects were unlikely attributable to off-target calcilytic actions on the parathyroid glands, as free ionised blood calcium levels were not altered for up to 24 hours after calcilytic inhalation. Together, these observations suggest that topically delivered calcilytics may represent a novel treatment strategy for COPD.
Author(s): Yarova PL, Davies C, Price SA, Huang Q, Graca JA, Maleki-Toyserkani S, Lowe APP, Kidd EJ, Ford WR, Broadley KJ, Ward JPT, Corrigan CJ, Prakash YS, Kemp PJ, Riccardi D
Publication type: Article
Publication status: Published
Journal: Respiratory Drug Delivery
Print publication date: 24/03/2016
Online publication date: 24/03/2016
Acceptance date: 30/03/2016
Publisher: RDD Online