M2048 Safety, Tolerability and Effects On Intestinal Permeability of Larazotide Acetate in Celiac Disease: Results of a Phase IIB 6-Week Gluten-Challenge Clinical Trial

Kelly, Ciarán P.; Green, Peter H.; Murray, Joseph A.; DiMarino, Anthony J.; Arsenescu, Razvan; Colatrella, Anthony M.; Leffler, Daniel A.; Jacobstein, Douglas; León, Francisco; Jiang, John; Fedorak, Richard N.

doi:10.1016/s0016-5085(09)62182-x

Cited by 11 publications

(7 citation statements)

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“…Combined, these data suggest that AT1001 is well tolerated and appears to reduce proinflammatory cytokine production and gastrointestinal symptoms in CD patients. AT1001 has now been tested in ϳ500 subjects with excellent safety profile and promising efficacy as concern protection against symptoms caused by gluten exposure in CD patients (85).…”

Section: Proof Of the Pathogenic Role Of Zonulin-mediated Intestinal mentioning

confidence: 99%

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Fasano

2011

Physiological Reviews

769

633

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The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.

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Section: Proof Of the Pathogenic Role Of Zonulin-mediated Intestinal mentioning

confidence: 99%

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Fasano

2011

Physiological Reviews

769

633

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“…Gastrointestinal symptoms were significantly more frequent among patients of the placebo group as compared to the Larazotide acetate group [54]. Larazotide acetate has now been tested in approximately 500 subjects with excellent safety profile and promising efficacy as concern protection against symptoms caused by gluten exposure in CD patients [55].…”

Section: Ankylosing Spondylitismentioning

confidence: 99%

Leaky Gut and Autoimmune Diseases

Fasano

2011

Clinic Rev Allerg Immunol

280

179

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Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases.

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“…[17][18][19] Modulators of intestinal permeability have been developed to diminish uptake of gluten peptides into the gastrointestinal mucosa. 20,21 Other experimental therapies include restoration of oral tolerance by administration of gluten peptides secreted by Lactococcus 22 and immunomodulation by helminths. 23 Finally, tissue transglutaminase inhibitors 24,25 to prevent peptide selective deamidation, HLA-DQ groove antagonists 26 to block the T-CD4 lymphocyte recognition, and inhibitors of adhesion molecules to hinder inflammatory cell recruitment 23 are also under development.…”

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confidence: 99%

The Copolymer P(HEMA-co-SS) Binds Gluten and Reduces Immune Response in Gluten-Sensitized Mice and Human Tissues

et al. 2012

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M2048 Safety, Tolerability and Effects On Intestinal Permeability of Larazotide Acetate in Celiac Disease: Results of a Phase IIB 6-Week Gluten-Challenge Clinical Trial

Cited by 11 publications

References 0 publications

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer

Leaky Gut and Autoimmune Diseases

The Copolymer P(HEMA-co-SS) Binds Gluten and Reduces Immune Response in Gluten-Sensitized Mice and Human Tissues

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