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.

A Low-Molecular-Weight Alginate Oligosaccharide Disrupts Pseudomonal Microcolony Formation and Enhances Antibiotic Effectiveness

“…(48); coadministration of alginate lyase with DNase, which has been reported to increase the efficacy of antibiotics in reducing biofilm growth (49); and coadministration of antibiotics with alginate lyase to eliminate mucoid variants not affected by antibiotics alone (50). Interestingly, we have also previously demonstrated synergy between OligoG CF-5/20 and recombinant human DNase I (rhDNase I) in modifying the mechanical and structural properties of CF sputum (31).…”

“…We previously described the use of a low-molecular-weight alginate oligomer (OligoG CF-5/20; Ն85% guluronic acid, with a degree of polymerization [DPn] of 16; number average molecular weight [Mn], 3,200) from the seaweed Laminaria hyperborea as a promising novel therapy in CF (29)(30)(31). In vitro studies demonstrated the ability of OligoG CF-5/20 to modify the bacterial surface charge (30) and biofilm growth of nonmucoid Pseudomonas spp.…”

A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

“…OligoG displays antibacterial properties in that it disrupts and inhibits biofilm formation as well as potentiates the action of certain antibiotics through its ability to directly bind to the bacterial surface [15][16][17][18]. Additionally, OligoG has been shown to bind mucin directly and disrupt interactions in complex mucus by reducing cross-linking within mucus [19][20][21][22]. The current study was undertaken to determine whether OligoG would decrease CF intestinal manifestations in CF mice through its ability to disrupt complex interactions within mucus.…”

Marine Alginate Oligosaccharides – A Promising Biomaterial: Current Use and Future Perspectives in Food Industry and Pharmaceutical Applications

“…In another research, Pritchard et al (2016) described a new class of safe oligosaccharide (OligoG), with the highly purified content (> 85 %) of guluronic acid. It currently is being evaluated as a treatment for chronic respiratory diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) [48].…”