Larazotide acetate
Alessio Fasano and his colleagues discovered that zonulin regulates intestinal permeability, which is also known as 'leaky gut' and allows celiac disease to occur. This discovery led his team to evaluate chemicals that would help the body maintain intestinal permeability to keep pathogenic proteins out of the body. While larazotide acetate affects intestinal permeability in lab rats, clinical trials so far indicate that it does not affect intestinal permeability in humans.
Clinical trials on the drug continue. Innovate Biopharmaceuticals, which owned the rights to larazotide, merged with RDD Pharma and is now 9 Meters. The company has completed trials of the drug on MIS-C (multi system inflammatory syndrome in children), a novel syndrome that surfaces after a COVID-19 infection.
Studies on larazotide acetate[edit]
- The safety, tolerance, pharmacokinetic and pharmacodynamic effects of single doses of AT-1001 in coeliac disease subjects: a proof of concept study https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1365-2036.2007.03413.x
- This 2007 paper for a small pilot study noted that larazotide improved intestinal permeability. "Following acute gluten exposure, a 70% increase in intestinal permeability was detected in the placebo group, while none was seen in the AT-1001 group."
- Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study https://doi.org/10.1111/apt.12147
- This 2012 paper noted that the study used the lactulose-to-mannitol (LAMA) ratio to measure intestinal permeability. "No significant differences in LAMA ratios were observed between larazotide acetate and placebo groups."
- A Randomized, Double-Blind Study of Larazotide Acetate to Prevent the Activation of Celiac Disease During Gluten Challenge https://dx.doi.org/10.1038%2Fajg.2012.211
- This 2012 paper noted: "The increase in LAMA ratio associated with the gluten challenge was not statistically significantly greater than the increase in the gluten-free control."
- Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial https://dx.doi.org/10.1053%2Fj.gastro.2015.02.008
- This 2015 paper noted that "results were mixed".
MIS-C related studies and recent studies:
- Multisystem inflammatory syndrome in children is driven by zonulin-dependent loss of gut mucosal barrier https://doi.org/10.1172/JCI149633
- This 2021 paper argues: "These mechanistic data on MIS-C pathogenesis provide insight into targets for diagnosing, treating, and preventing MIS-C, which are urgently needed for this increasingly common severe COVID-19–related disease in children."
- Larazotide acetate: a pharmacological peptide approach to tight junction regulation https://doi.org/10.1152/ajpgi.00386.2020
- In silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate https://doi.org/10.3389/fchem.2020.628609
- The Therapeutic use of the Zonulin Inhibitor AT-1001 (Larazotide) for a Variety of Acute and Chronic Inflammatory Diseases https://doi.org/10.2174/0929867328666210104110053
Zonulin:
- Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer https://doi.org/10.1152%2Fphysrev.00003.2008
Interviews:
- https://www.youtube.com/watch?v=3wUQOwpSkgU - Interview between Amy Proal and Alessio Fasano. Fasano and his colleagues discovered zonulin. Fasano's academic paper disclose his commercial interest in the success of larazotide.