Novel Therapies to Inhibit Mucus Synthesis and Secretion in Airway Hypersecretory Diseases

Abstract

Background: In asthma and chronic obstructive pulmonary disease (COPD), airway mucus hypersecretion contributes to impaired mucociliary clearance, mucostasis and, potentially, the development of mucus plugging of the airways. Summary: Excess mucus production can be targeted via therapies that focus on inhibition mucin synthesis, via reducing expression of mucin (MUC) genes, and/or inhibition of mucin secretion into the airways. Key Messages: This review discusses a number of therapeutic approaches to reduce airway mucus in asthma and COPD, including the use of synthetic and natural products. In particular, it highlights areas where clinical trials of inhibitors of particular target molecules are lacking. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are an example of a targeted therapy that has been researched to reduce mucus synthesis, as have inhibitors of EGFR's downstream signalling pathways, for example, mitogen-activated protein kinase-13 and hypoxia inducible factor-1. However, their efficacy and safety profiles are currently not up to the mark. There is clinical potential in Bio-11006, which reduces mucus secretion via the inhibition of myristoylated alanine-rich C-kinase substrate and is currently in Phase IIb trial.

Physicochemical properties of mucus and their impact on transmucosal drug delivery

“…Investigating the role of mucins both in health and disease has been of great interest, and from substantial progress in the past two decades. Specific mucins decreased production, secretion, and expression are potential novel strategies being evaluated for the treatment of pathologic mucus in airway inflammatory diseases (Bae et al, 2014; Dickinson et al, 2016; Fahy and Dickey, 2010; Ha and Rogers, 2016; Lee et al, 2016). …”

Effects of cannabis oil extract on immune response gene expression in human small airway epithelial cells (HSAEpC): implications for chronic obstructive pulmonary disease (COPD)

“…CLCA1 encodes chloride channel accessory 1, whose expression or up-regulation has been related to mucus overproduction as well as airway hyperreactivity in COPD (Hauber et al 2005;Iwashita et al 2012;Sala-Rabanal et al 2015;Wang et al 2007). The feasibility of inhibiting mucin production genes as a viable approach to treating COPD has been postulated (Ha and Rogers 2016). Accordingly, the use of cannabis oil extract to inhibit the expression of mucin production genes such as CLCA1 could help in controlling airway mucus hypersecretion.…”

Estrategias actuales en el manejo de las secreciones traqueobronquiales

“…No obstante, hasta el momento no existen estudios que demuestren que tenga la misma eficacia en pacientes con enfermedades respiratorias. 18,19 Mucocinéticos Comúnmente referidos como fármacos que mejoran el aclaramiento de la tos al actuar de forma directa en el latido ciliar. Es importante mencionar que no se ha demostrado un efecto consistente sobre el aclaramiento mucociliar en pacientes con historia de enfermedad pulmonar crónica.…”