Inhibition of gliadin peptides
Novel compounds and methods for the inhibition of biological barrier permeability and for the inhibition of peptide translocation across biological barriers are identified. Assays for determining modulators of biological barrier permeability and for peptide translocation across biological barriers are provided. Methods for treating diseases relating to aberrant biological barrier permeability and peptide translocation across biological barriers are provided. Such diseases include celiac disease, necrotizing enterocolitis, diabetes, cancer, inflammatory bowel diseases, asthma, COPD, excessive or undesirable immune response, gluten sensitivity, gluten allergy, food allergy, rheumatoid arthritis, multiple sclerosis, immune-mediated or type 1 diabetes mellitus, systemic lupus erythematosus, psoriasis, scleroderma and autoimmune thyroid diseases.
1. A method for treating loss of intestinal epithelial barrier integrity associated with an acute intestinal inflammatory attack in a patient having Celiac Disease, the method comprising: administering the peptide of SEQ ID NO:1 to the intestine of said patient a plurality of times per day for a plurality of days about 48 hours after the acute intestinal inflammatory attack, wherein the acute inflammatory attack involves factors that cause increased permeability of intestinal cells, and wherein the patient is undergoing therapy with an anti-inflammatory agent selected from an anti-inflammatory steroid or non-steroidal anti-inflammatory agent, and wherein the peptide is formulated with a delayed release coating that is substantially stable in gastric fluid and substantially unstable in intestinal fluid.
2. The method of claim 1 , wherein the anti-inflammatory agent is aspirin or aminosalicylate.
3. The method of claim 1 , wherein the anti-inflammatory agent is a corticosteroid.
4. The method of claim 1 , wherein the peptide is administered in a delayed release composition.
5. The method of claim 4 , wherein the composition releases 70% or more by weight of the peptide within 30 to 90 minutes of exposure to pH of greater than 5.