PRE-CLINICAL RESEARCH AND DEVELOPMENT

Pre-clinical research has focussed on the mucolytic activity of heparin. Patients with obstructive inflammatory airways diseases, such as COPD and cystic fibrosis, often have abnormally high levels of extracellular DNA in the airway secretions (Figure 1A), that form a polymeric network contributing to the viscosity of the secretions making them difficult to expectorate. Retained secretions limit the delivery of inhaled drugs that target the airway epithelium and underlying tissues, and invite infection that further promote the inflammatory response. DNA also inhibits the activity of a number of antibiotics and supports the growth of bacterial biofilm, therefore the removal of extracellular DNA is a clinical imperative.

Ockham's research has shown that, when treated with heparin (Figure 1B and C) DNA networks dissolve and the thinned mucus is more easily expectorated. This is in part due to the activation of endogenous DNase I. Our research has also shown that heparin activates DNase I added exogenously to DNA networks (Broughton-Head et al . 2007, see publications).

The described effect leads to the opportunity to improve mucus clearance and the delivery of other inhaled drugs, including corticosteroids and bronchodilators, to underlying cells and tissues.

Figure 1;
A