Innovate's lead drug candidate, larazotide acetate, has a mechanism of action that renormalizes the dysfunctional intestinal barrier by decreasing intestinal permeability and reducing antigen trafficking, such as
gliadin fragments in celiac disease, and bacterial toxins and immunogenic antigens in NASH.
After exposure to gluten, specific antibodies as TG2 (anti-transglutaminase antibodies), EMA (anti-endomysial antibodies) and DGP (deamidated
gliadin peptide antibodies) are synthesized, causing an autoimmune inflammatory reaction, leading to an atrophy of villi of the small intestinal mucosa [2].
Gliadin, which is wheat prolamin, is mainly responsible for immunopathogenesis (1).
Separation of
Gliadin and Glutenin from wheat flour:
Gliadins were isolated from wheat flour by mixing 400mg of grinded flour with 2ml of 50% isopropanol.
Tissue Transglutaminase (TTG) TTG IgA no Celiac disease TTG IgG no Celiac disease Deamidated
Gliadin Peptide (DGP) DGP IgA no Celiac disease DGP IgG no Celiac disease Anti-gliadin Antibody (AGA) AGA IgA no Celiac disease AGA IgG no Celiac disease/NCGS Endomysial Antibody IgA no Celiac disease Wheat specific IgE no Wheat llerqy (IqE) HLA DQ2 and DQ8 yes Celiac disease/NCGS Lab Test Sensitivity Specificity Tissue Transglutaminase (TTG) TTG IgA 98% 98% TTG IgG 70% 95% Deamidated
Gliadin Peptide (DGP) DGP IgA 88% 95% DGP IgG 80% 98% Anti-gliadin Antibody (AGA) AGA IgA 85% 90% AGA IgG 85% (CD) 80% (CD) Endomysial Antibody IgA 95% 99% Wheat specific IgE 83% 43% HLA DQ2 and DQ8 rv100% low; varies (CD) depending on population
Some triggers for excessive release of zonulin include
gliadin, inflammation, direct adherence of any bacteria to EC, excessive LPS, bacterial enterotoxins, excessive fructose, and possibly some industrial food additives.
Clinical comprehensive evaluation by allergists used as the reference gold standard, receiver operator characteristic (ROC) curves were plotted, areas under curve (AUC) for specific immunoglobin E (sIgE) were compared to evaluate the diagnostic value of IgE specific to wheat, gluten, and ?-5
gliadin. Patients were followed up by telephone questionnaire 1 year after diagnosis.
A clinical dietician at Dow University of Health and Sciences and member of Pakistan Nutrition and Dietetic Society (PNDS), Badder Hina, said all wheat flour naturally contains two proteins: gluten and
gliadin. Gluten contains elasticity which makes flour/chappati to expand.
[43], based on previously reported cross-reactivity of antibodies to
gliadin with the enamel proteins, amelogenin and ameloblastin, investigated the ability of anti-gliadin IgG to recognize enamel organ structures.
[29] report that
gliadin solutions in propanol 50% (v/v) are classified as Newtonian fluids, but
gliadin solutions possess shear-thinning behavior (pseudoplastic behavior) when they maintain a pH of 2.0-8.
They can be synthesized from various protein including water soluble proteins (e.g., bovine and human serum albumin) and insoluble protein (e.g., zein and
gliadin).