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MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (\u03b2ENaC-Tg mice).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G\u2032) of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in \u03b2ENaC-Tg mice to determine its mucolytic efficacy\n                      <jats:italic>in vivo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G\u2032, was faster in decreasing sputum G\u2032 by 50% and caused mucolysis of a larger proportion of sputum samples within 15\u2005min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1\u2005day in adult \u03b2ENaC-Tg mice decreased airway mucus content (16.8\u00b13.2\n                      <jats:italic>versus<\/jats:italic>\n                      7.5\u00b11.2\u2005nL\u00b7mm\n                      <jats:sup>\u22122<\/jats:sup>\n                      , p&lt;0.01) and bronchoalveolar lavage cells (73\u2009833\u00b16930\n                      <jats:italic>versus<\/jats:italic>\n                      47\u2009679\u00b17736 cells\u00b7mL\n                      <jats:sup>\u22121<\/jats:sup>\n                      , p&lt;0.05). Twice-daily treatment with MUC-031 for 2\u2005weeks also caused decreases in these outcomes in adult and neonatal \u03b2ENaC-Tg mice and reduced mortality from 37% in vehicle-treated \u03b2ENaC-Tg neonates to 21% in those treated with MUC-031 (p&lt;0.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in \u03b2ENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.02022-2022","type":"journal-article","created":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T11:03:18Z","timestamp":1681988598000},"page":"2202022","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":40,"title":["A novel thiol-saccharide mucolytic for the treatment of muco-obstructive lung diseases"],"prefix":"10.1183","volume":"61","author":[{"given":"Annalisa","family":"Addante","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfred","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Gitlin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabelle","family":"Charbit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Orain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron 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