The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases.

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, 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 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 treatment. Moreover, new possible molecular targets for this molecule have also been demonstrated.