The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases.
This systematic review examines the role of the zonulin pathway in regulating tight junction integrity and its contribution to increased epithelial and endothelial permeability across a range of chronic and acute inflammatory conditions. The authors searched PubMed and Google Scholar using terms related to Larazotide (also known as AT-1001, FZI/0, and INN-202), retrieving 209 publications, which were then filtered for relevance and English language. Findings were organized by disease area, including celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory diseases (both infectious and non-infectious), and miscellaneous conditions. The review concludes that evidence from both in vivo and in vitro studies supports a substantial role for zonulin dysregulation in these diseases, and suggests Larazotide — a zonulin antagonist — as a potentially viable therapeutic strategy. The authors also highlight newly identified molecular targets for Larazotide. Key limitations include the heterogeneity of the underlying studies (spanning animal models, in vitro work, and human trials of varying quality), and the review's broad scope may obscure differences in evidence quality across disease indications.
Why this grade: This is a systematic narrative review synthesizing heterogeneous preclinical and clinical literature; it does not generate primary human data, so evidence grade is classified as review.
Background The involvement of intercellular tight junctions and, in particular, the modulation of their competency by the zonulin pathway with a subsequent increase in epithelial and endothelial permeability, has been described in several chronic and acute inflammatory diseases. In this scenario, Larazotide, a zonulin antagonist, could be employed as a viable therapeutic strategy. Objective The present review aims to describe recent research and current observations about zonulin involvement in several diseases and the use of its inhibitor Larazotide for their treatment. Methods A systematic search was conducted on PubMed and Google Scholar, resulting in 209 publications obtained with the following search query: "Larazotide," "Larazotide acetate," "AT-1001," "FZI/0" and "INN-202." After careful examination, some publications were removed from consideration because they were either not in English or were not directly related to Larazotide. Results The obtained publications were subdivided according to Larazotide's mechanism of action and different diseases: celiac disease, type 1 diabetes, other autoimmune diseases, inflammatory bowel disease, Kawasaki disease, respiratory (infective and/or non-infective) diseases, and other. Conclusion A substantial role of zonulin in many chronic and acute inflammatory diseases has been demonstrated in both in vivo and in vitro, indicating the possible efficacy of a Larazotide treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.
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