A novel glycopolymer improves abnormal cystic fibrosis mucus

Research output: Contribution to journalArticle

  • External authors:
  • Courtney M. Fernanadez-Petty
  • Gareth Hughes
  • Hannah L. Bowers
  • John D. Watson
  • Bradley H. Rosen
  • Stacy M. Townsend
  • Carlos Santos
  • Kengyeh K. Chu
  • Susan E. Birket
  • Yao Li
  • Hui Min Leung
  • Marina Mazur
  • Bryan A. Garcia
  • T. Idil Apak Evans
  • Emily Falk Libby
  • Heather Hathorne
  • Justin Hanes
  • Guillermo J. Tearney
  • John P. Clancy
  • John F. Engelhardt
  • William E. Swords
  • William P. Wiesmann
  • Shenda M. Baker
  • Steven M. Rowe

Abstract

Cystic fibrosis (CF) is characterized by increased mucus viscosity and delayed mucociliary clearance that contributes to progressive lung function decline. Mucus in the respiratory and GI tract is excessively adhesive in the presence of airway dehydration and excess extracellular Ca2+upon mucin release, promoting hyperviscous, densely packed mucins, characteristic of CF. Therapies that target mucins directly through ionic interactions remain unexploited. Here we show that poly (acetyl, arginyl) glucosamine (PAAG), a novel polycationic biopolymer suitable for human use, interacts directly with mucins in a Ca2+-sensitive manner to reduce CF mucus viscoelasticity and improve its transport. Notably, PAAG induced linear structure of purified MUC5B and altered its sedimentation profile and viscosity, indicative of proper mucin expansion. In vivo, PAAG nebulization improved mucociliary transport in CF rats with delayed mucus clearance and cleared mucus plugging in CF ferrets. As a demonstration of a synthetic glycopolymer for the potential treatment of human disease, and to exploit ion displacement to target aberrant mucin structure, PAAG represents a novel molecular agent that may benefit a broad array of mucus diseases.

Bibliographical metadata

Original languageEnglish
JournalJournal of Clinical Investigation Insight
Publication statusAccepted/In press - 27 Feb 2019

Related information

Researchers

View all