About Muco – Obstructive Lung (Pulmonary) Diseases

The spectrum of lung diseases that affect the airways, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, primary ciliary dyskinesia, and non–cystic fibrosis bronchiectasis, can be characterized as muco-obstructive diseases. These diseases have the clinical features of cough, sputum production, and episodic exacerbations that are often associated with a diagnosis of chronic bronchitis.

Human airway mucus is a hydrogel composed of approximately 98% water and 2% solids including high-molecular-weight mucin polymers. The two major synthesized and secreted respiratory mucins, MUC5B and MUC5AC, are physically very large proteins and a critical part of mucus. In healthy persons, a well-hydrated mucus layer is transported rapidly (from the distal airways toward the trachea). In muco-obstructive diseases hyper-concentrated (dehydrated) mucus, failed mucus transport, and mucus adhesion to airway surfaces is observed. Mucus in the small airways cannot be cleared by cough and accumulates, forming airflow obstruction, infection, and inflammation (Bucher et al 2019).

Mucin concentrations are abnormally raised in muco-obstructive diseases like COPD, cystic fibrosis, primary ciliary dyskinesia, and non–cystic fibrosis bronchiectasis — and these findings are consistent with a role for elevated mucin concentrations in the pathogenesis of muco-obstructive disease.

Bucher et al 2019

SpliSense is developing  Antisense Oligonucleotides (ASOs) that can modulate and lower MUC5AC and/or MUC5B expression and production in a specific manner and thus potentially reduce mucin levels in mucus, decrease mucus viscosity and accumulation in the airways, and reduce infection and inflammation.

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