2016
DOI: 10.1016/j.jcf.2016.06.005
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A novel guluronate oligomer improves intestinal transit and survival in cystic fibrosis mice

Abstract: OligoG improves intestinal transit and survival in CF mice by reducing the accumulation of intestinal mucus. OligoG's ability to directly bind mucin, disrupt mucin interaction and/or sequester calcium allowing for mucin expansion may explain the decrease in mucus accumulation.

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Cited by 24 publications
(21 citation statements)
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“…CF mice on a liquid diet [32, 33] or a solid diet with an osmotic laxative in the water [34] have a significant reduction in intestinal obstruction, but still display reduced growth. Similarly, treatment with a novel guluronate oligomer, OligoG, which reduces intestinal mucus accumulation, improved survival in CF mice, but did not restore normal growth [35]. In addition, genetic approaches to reduce intestinal obstruction in CF models have not resulted in a normal growth profile.…”
Section: Resultsmentioning
confidence: 99%
“…CF mice on a liquid diet [32, 33] or a solid diet with an osmotic laxative in the water [34] have a significant reduction in intestinal obstruction, but still display reduced growth. Similarly, treatment with a novel guluronate oligomer, OligoG, which reduces intestinal mucus accumulation, improved survival in CF mice, but did not restore normal growth [35]. In addition, genetic approaches to reduce intestinal obstruction in CF models have not resulted in a normal growth profile.…”
Section: Resultsmentioning
confidence: 99%
“…The use of a small glycopolymers to chelate Ca 2+ as a means to favorably alter mucus viscoelasticity in CF lung disease has been investigated recently (10)(11)(12). While this is mechanistically related to the effects described here, the use of a high-MW glycopolymer that interacts directly with mucins and the glycocalyx to displace Ca 2+ binding is a distinct approach.…”
Section: Discussionmentioning
confidence: 99%
“…In the absence of an environment rich in bicarbonate and sodium to remove and displace Ca 2+ , as occurs in the event of dysfunctional CF transmembrane regulator-mediated (CFTR-mediated) ion transport in CF and other lung diseases, mucins are unable to undergo normal posttranslational processing and expansion to their linear form, instead remaining compact, contributing to mucus that is hyperviscous, cohesive, and adhesive to the surface epithelium (7)(8)(9). Ca 2+ chelation has been investigated as an intervention to change the local ionic environment of airway mucus but has not yet been successful (7,(10)(11)(12)(13). In contrast, we postulated that a polycationic glycopolymer could modulate the mucin-mucin interactions mediated by Ca 2+ to create a solution phase of mucus with different adhesive and viscoelastic properties.…”
Section: Introductionmentioning
confidence: 99%
“…Alginate, which disrupts the mucin-mucin interaction or the chelation of calcium ions (Ambort et al 2012), can be utilized to reduce the accumulation of intestinal mucus in mice with cystic fibrosis (CF). Vitko et al (2016) evaluated the therapeutic effect of alginate oligosaccharide, OligoG, on the CF mouse model. CF is caused by a mutation in the gene that encodes the CF transmembrane conductance regulator protein.…”
Section: Anti-cystic Fibrosis Activitymentioning
confidence: 99%