Larazotide acetate regulates epithelial tight junctions in vitro and in vivo

Gopalakrishnan, Sandeep; Durai, Malarvizhi; Kitchens, Kelly M.; Tamiz, Amir P.; Somerville, Robert; Ginski, Mark; Paterson, Blake M.; Murray, Joseph A.; Verdú, Elena F.; Alkan, Şefik Ş.; Pandey, Niranjan B.

doi:10.1016/j.peptides.2012.02.015

Cited by 97 publications

(81 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, larazotide acetate mediated these effects in a dose-dependent manner. Larazotide acetate also inhibited paracellular permeability by AT-1002 in a dose-dependent manner [Gopalakrishnan et al 2009[Gopalakrishnan et al , 2012a. larazotide acetate on the apical side of the cells (at concentrations as low as 0.1 mM) reduced passage of FITC-labeled gliadin peptides through the epithelial cell [Watts et al 2005;Arrieta et al 2006].…”

Section: In Vitro Effects Of Larazotide Acetatementioning

confidence: 91%

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate

Khaleghi

Lamba

et al. 2015

Therap Adv Gastroenterol

Self Cite

View full text Add to dashboard Cite

Celiac disease (CD) is a common chronic immune disease triggered by gluten. Gliadin peptides pass through the epithelial layers, either paracellularly or transcellularly, to launch a potent adaptive immune response in the lamina propria. This aberrant immune response leads to diverse gastrointestinal and extra-gastrointestinal symptoms. Currently, the only treatment for CD is a strict lifelong adherence to a gluten-free diet (GFD), which can be challenging. An early effect of gluten in CD is an increase in gut permeability. Larazotide acetate, also known as AT-1001, is a synthetic peptide developed as a permeability regulator primarily targeting CD. In vitro studies indicate that larazotide acetate is capable of inhibiting the actin rearrangement caused by gliadin and clinical studies have been conducted using this peptide as a therapy for CD.

show abstract

Section: In Vitro Effects Of Larazotide Acetatementioning

confidence: 91%

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate

Khaleghi

Lamba

et al. 2015

Therap Adv Gastroenterol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Larazotide acetate (AT-1001, Alba Pharmaceuticals) is a peptidic tight junction regulator that was shown to preserve tight junction structure of the intestinal epithelium both in vitro and in gliadin-sensitized mice upon gliadinadministration (51). In a recently reported phase IIa study (NCT00362856), larazotide acetate was applied in capsules before a gluten-containing meal thrice per day for 14 days (2.4 g of gluten/day in total) (52).…”

Section: Modulator Of Paracellular Permeabilitymentioning

confidence: 99%

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

2012

View full text Add to dashboard Cite

Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a glutenfree diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.

show abstract

“…(4) As of now, there is no convincing evidence that an intervention that restores or improves barrier function in man can alter the natural history of a given disease or disorder. Though some encouraging data have emerged regarding the use of larazotide acetate, a regulator of tight junctional function [36], as adjunctive therapy in celiac disease [37 && ], tight junctional regulation remains an exciting goal rather than an already attained achievement in human disease [38,39]. Nonetheless, there are substantial pieces of circumstantial evidence that point to a more fundamental role for the barrier in certain disease states.…”

Section: Gut Barrier Function In Diseasementioning

confidence: 99%

Leaky gut – concept or clinical entity?

Quigley

2016

Current Opinion in Gastroenterology

107

View full text Add to dashboard Cite

Although several aspects of barrier function can be assessed in man, one must be aware of exactly what a given test measures, as well as of its limitations. The temptation to employ results from a test of paracellular flux to imply a role for barrier dysfunction in disorders thought to be based on bacterial or macromolecular translocation must be resisted. Although changes in barrier function have been described in several gastrointestinal disorders, their primacy remains to be defined. At present, few studies support efficacy for an intervention that improves barrier function in altering the natural history of a disease process.

show abstract

Larazotide acetate regulates epithelial tight junctions in vitro and in vivo

Cited by 97 publications

References 46 publications

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate

The potential utility of tight junction regulation in celiac disease: focus on larazotide acetate

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

Leaky gut – concept or clinical entity?

Contact Info

Product

Resources

About