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The Role of Zonulin and Intestinal Permeability in Celiac Disease

Celiac.com 11/08/2005 - Today a team of scientists at Alba Therapeutics Corporation (Alba) and the University of Maryland School of Medicine reported a direct link between gluten-induced intestinal permeability and zonulin in tissues from patients with celiac disease. The investigators were able to successfully prevent gluten-induced intestinal tissue leak with the administration of the zonulin antagonist FZI/0 (AT-1001). AT-1001 is an orally administered peptide currently under development for the treatment of celiac disease.

Published in the November issue of the Scandinavian Journal of Gastroenterology, these results describe the role that leaky gut plays in celiac disease and the role that zonulin plays in establishing the leak. These results are another milestone towards understanding the role of zonulin in celiac disease, says Alessio Fasano, M.D., lead author of the paper, professor of pediatrics, medicine and physiology at the University of Maryland School of Medicine and director of its Center for Celiac Research.

These results reinforce our conviction that AT-1001 has great therapeutic potential and we look forward to confirming these observations in celiac patients soon, stated Alba CEO Dr. Blake M. Paterson.

About Zonulin
Zonulin is a signaling protein that transiently and reversibly opens the tight junctions (tj) between the cells of epithelial and endothelial tissues such as the intestinal mucosa, blood brain barrier and pulmonary epithelia. Zonulin appears to be involved in many diseases in which leakage occurs via paracellular transport across epithelial and endothelial tight junctions (tj),
and thus may play an important potential role in the treatment of autoimmune diseases.

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About Celiac Disease
Celiac disease is a T-cell mediated auto-immune disease that occurs in genetically susceptible individuals and is characterized by small intestinal inflammation, injury and intolerance to gluten. According to the National Institutes of Health, celiac disease affects approximately 3 million Americans, although the diagnosis is rarely made. The only treatment for celiac disease is complete elimination of gluten from the diet, which results in remission for some patients.

About Alba
Alba Therapeutics Corporation is a privately held biopharmaceutical company based in Baltimore, Maryland. Alba is dedicated to commercializing disease-modifying therapeutics and drug delivery adjuvants based on the zonulin pathway. Albas lead molecule, AT-1001, is targeted towards the treatment of celiac disease and other auto-immune illnesses.

Contact: Dr. Blake Paterson
Alba Therapeutics Corporation
(410) 522-8708

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By the way, I got my biopsy pathology report and the doctor took 2 biopsies, not the recommended 4-6. It says no "significant villous blunting not seen." I don't know if I should laugh or cry---so frustrating.

Thank you, this does feel helpful and reassuring. Did you end up getting blood tests again after going gluten-free? Do you have to worry about cross contamination as much as with a celiac diagnosis? How do you explain it to friends and family? Non-Celiac gluten sensitivity sounds so vague and I know it's dumb, but I worry about people not taking me seriously.

Helen, a woman with severe lifelong eczema/dermatitis, wrote to me a few weeks ago, saying "I have taken your advice and been strictly gluten free for five months now. The eczema inflammation is 99% gone and my skin quality has significantly improved. I do still get a bit itchy around my neck area and elbow creases, more so at night when it is warm. I have noticed a significant improvement in my asthma also. I still use antihistamines perhaps once or twice a week for runny nose. Does this mean I will need to be gluten free for life? Which of your books would you say would be the most relevant for someone in my position? Thank you for your assistance, regards, Helen. View the full article

Hello and welcome Reading your post it looks like each of your results were within the 'normal' range. There doesn't appear to be mention of a total serum IGA to make sure you have enough of this to begin with to make the test accurate however - but there are others here who are more experienced who may be able to tell you more. There are some other celiac tests: tTG IgA and tTG IgG -DGP IgA and DGP IgG -EMA IgA -total serum IgA and IgG (control test to ensure tests are not false negatives) They may not be covered by your provider however. Note that you appear to have been avoiding gluten somewhat already, that could impact on the tests accuracy. Your symptoms sound like they could be gluten related (but then practically everything could!) but you may want to discuss with your doctor whether to push for further testing or move to trial gluten free diet. Some people, like myself, test negative but still find symptoms respond to gluten free. Best of luck!

There's a great post by Tarnalberry in that thread.