Polysulfated Hyaluronan GM-1111 Inhibits Elastase and Improves Rheology in CF Sputum.

Polysulfated Hyaluronan GM-1111 Inhibits Elastase and Improves Rheology in CF Sputum. Am J Respir Cell Mol Biol. 2020 Dec 02;: Authors: Kummarapurugu AB, Zheng S, Pulsipher A, Savage JR, Ma J, Rubin BK, Kennedy TP, Voynow JA Abstract Cystic fibrosis (CF) lung disease is marked by high concentrations of neutrophil elastase (NE) and DNA polymers; both factors contribute to airway disease. Although inhaled recombinant human dornase alfa reduces the frequency of CF pulmonary exacerbations, it also increases free NE activity in the sputum. There are no approved anti-NE therapies for patients with CF. We investigated whether synthetic, low molecular weight polysulfated hyaluronan (GM-1111) would be effective as an anti-NE drug using ex vivo CF sputum. Anti-NE activity of GM-1111 was tested in CF sputum in the presence or absence of dornase alfa and/or hypertonic saline, using a spectrophotometric assay specific for human NE, and compared to unfractionated heparin. We tested whether GM-1111 disaggregated DNA from CF sputum by gel electrophoresis analysis, or modified CF sputum viscoelastic properties using a dynamic rheometer. GM-1111 and unfractionated heparin had near equivalent anti-NE activity in CF sputum in the presence of dornase alfa. Both GM-1111 and unfractionated heparin retained anti-NE activity in hypertonic saline, but with decreased activity. GM-1111 increased release of soluble DNA in CF sputum, resulting in improved depolym...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Tags: Am J Respir Cell Mol Biol Source Type: research