title: A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease.
abstract: The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12-15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF-5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Human studies showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF.
authors.affiliation: Advanced Therapies Group, School of Dentistry, Cardiff University , Cardiff CF14 4XY, U.K.
authors.forename: Manon F
authors.initials: MF
authors.lastname: Pritchard
authors.affiliation: Advanced Therapies Group, School of Dentistry, Cardiff University , Cardiff CF14 4XY, U.K.
authors.forename: Lydia C
authors.initials: LC
authors.lastname: Powell
authors.forename: Georgina E
authors.initials: GE
authors.lastname: Menzies
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lewis
authors.forename: Karl
authors.initials: K
authors.lastname: Hawkins
authors.forename: Chris
authors.initials: C
authors.lastname: Wright
authors.affiliation: Respiratory/Cystic Fibrosis Unit, Children's Hospital for Wales , Cardiff CF14 4XW, U.K.
authors.forename: Iolo
authors.initials: I
authors.lastname: Doull
authors.affiliation: Medical Microbiology, School of Medicine, College of Biomedical and Life Sciences, Cardiff University , Cardiff CF14 4EP, U.K.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Walsh
authors.affiliation: AlgiPharma AS, Sandvika 1337, Norway.
authors.forename: Edvar
authors.initials: E
authors.lastname: Onsøyen
authors.affiliation: AlgiPharma AS, Sandvika 1337, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Dessen
authors.affiliation: AlgiPharma AS, Sandvika 1337, Norway.
authors.forename: Rolf
authors.initials: R
authors.lastname: Myrvold
authors.affiliation: AlgiPharma AS, Sandvika 1337, Norway.
authors.forename: Philip D
authors.initials: PD
authors.lastname: Rye
authors.affiliation: AlgiPharma AS, Sandvika 1337, Norway.
authors.forename: Astrid H
authors.initials: AH
authors.lastname: Myrset
authors.affiliation: Bio-Images Drug Delivery Ltd., Glasgow G4 0SF, U.K.
authors.forename: Howard N E
authors.initials: HN
authors.lastname: Stevens
authors.affiliation: Bio-Images Drug Delivery Ltd., Glasgow G4 0SF, U.K.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hodges
authors.affiliation: Gartnavel Hospital, Glasgow G12 0YN, U.K.
authors.forename: Gordon
authors.initials: G
authors.lastname: MacGregor
authors.affiliation: Glasgow Royal Infirmary, Glasgow G4 0ET, U.K.
authors.forename: James B
authors.initials: JB
authors.lastname: Neilly
authors.affiliation: Advanced Therapies Group, School of Dentistry, Cardiff University , Cardiff CF14 4XY, U.K.
authors.forename: Katja E
authors.initials: KE
authors.lastname: Hill
authors.affiliation: Advanced Therapies Group, School of Dentistry, Cardiff University , Cardiff CF14 4XY, U.K.
authors.forename: David W
authors.initials: DW
authors.lastname: Thomas
mesh_terms: D000293:Adolescent; D000328:Adult; D000464:Alginates / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D017321:Clinical Trials, Phase I as Topic; D003550:Cystic Fibrosis / Q000188:drug therapy*; D005260:Female; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D018625:Microscopy, Atomic Force; D008855:Microscopy, Electron, Scanning; D009077:Mucins / Q000737:chemistry* / Q000378:metabolism; D009093:Mucus / Q000737:chemistry* / Q000378:metabolism; D009844:Oligosaccharides / Q000737:chemistry* / Q000378:metabolism; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D017550:Spectroscopy, Fourier Transform Infrared; D013183:Sputum / Q000737:chemistry; D013552:Swine; D055815:Young Adult
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D009077:Mucins; D009844:Oligosaccharides; D011108:Polymers; D020723:Glucuronic Acid
keywords: alginate; cystic fibrosis; mucin; polymer therapy; safety; sputum; viscoelasticity