ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2023
SNSP113 (PAAG) improves mucociliary transport and lung pathology in the Scnn1b-Tg murine model of CF lung disease.
Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 5 citations in OpenAlex.
- Generative active learning guided discovery of a tobramycin and ciprofloxacin adjuvant against multidrug-resistantActa pharmaceutica Sinica. B · 2026Article
- Mucins and Their Roles in Asthma.Immunological reviews · 2025Review
- Emerging cell and molecular targets for treating mucus hypersecretion in asthma.Allergology international : official journal of the Japanese Society of Allergology · 2024Review
- Nontuberculous Mycobacteria, Mucociliary Clearance, and Bronchiectasis.Microorganisms · 2024Review
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7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMucus stasis, a hallmark of muco-obstructive disease, results from impaired mucociliary transport and leads to lung function decline and chronic infection. Although therapeutics that target mucus stasis in the airway, such as hypertonic saline or rhDNAse, show some therapeutic benefit, they do not address the underlying electrostatic defect apparent in mucins in CF and related conditions. We have previously shown poly (acetyl, arginyl) glucosamine (PAAG, developed as SNSP113), a soluble, cationic polymer, significantly improves mucociliary transport in a rat model of CF by normalizing the charge defects of CF mucin. Here, we report efficacy in the CFTR-sufficient, ENaC hyperactive, Scnn1b-Tg mouse model that develops airway muco-obstruction due to sodium hyperabsorption and airway dehydration.
methodsScnn1b-Tg mice were treated with either 250 µg/mL SNSP113 or vehicle control (1.38% glycerol in PBS) via nebulization once daily for 7 days and then euthanized for analysis. Micro-Optical Coherence Tomography-based evaluation of excised mouse trachea was used to determine the effect on the functional microanatomy. Tissue analysis was performed by routine histopathology.
resultsNebulized treatment of SNSP113 significantly improved mucociliary transport in the airways of Scnn1b-Tg mice, without altering the airway surface or periciliary liquid layer. In addition, SNSP113 significantly reversed epithelial hypertrophy and goblet cell metaplasia. Finally, SNSP113 significantly ameliorated eosinophilic crystalline pneumonia and lung consolidation in addition to inflammatory macrophage influx in this model.
conclusionOverall, this study extends the efficacy of SNSP113 as a potential therapeutic to alleviate mucus stasis in muco-obstructive diseases in CF and potentially in related conditions.
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