Proteins for the treatment of epithelial barrier function disorders
The disclosure relates to therapeutic proteins and pharmaceutical compositions comprising said proteins, which have utility in treating various human diseases. In particular aspects, the disclosed therapeutic proteins are useful for treating human gastrointestinal inflammatory diseases and gastrointestinal conditions associated with decreased epithelial cell barrier function or integrity. Further, the disclosed therapeutic proteins are useful for treating human inflammatory bowel disease, including inter alia, Crohn's disease and ulcerative colitis.
1. A method of treating a gastrointestinal epithelial cell barrier function disorder, comprising:
administering to a patient in need thereof a pharmaceutical composition, comprising:
i. a therapeutic protein comprising an amino acid sequence having at least about 90% sequence identity to the sequence set forth in SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:13 or SEQ ID NO:19; and
ii. a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the gastrointestinal epithelial cell barrier function disorder is a disease associated with decreased intestinal epithelium integrity.
3. The method of claim 1 , wherein the gastrointestinal epithelial cell barrier function disorder is at least one selected from the group consisting of: inflammatory bowel disease, Crohn's disease, ulcerative colitis, pouchitis, irritable bowel syndrome, enteric infections, Clostridium difficile infections, metabolic diseases, obesity, type 2 diabetes, non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, liver disorders, alcoholic steatohepatitis, celiac disease, necrotizing enterocolitis, gastro intestinal disorders, short bowel syndrome, GI mucositis, chemotherapy induced mucositis, radiation induced mucositis, oral mucositis, interstitial cystitis, neurological disorders, cognitive disorders, Alzheimer's, Parkinson's, multiple sclerosis, autism, chemotherapy associated steatohepatitis (CASH), and pediatric versions of the aforementioned diseases.
4. The method of claim 1 , wherein the gastrointestinal epithelial cell barrier function disorder is inflammatory bowel disease.
5. The method of claim 1 , wherein the gastrointestinal epithelial cell barrier function disorder is Crohn's disease.
6. The method of claim 1 , wherein the gastrointestinal epithelial cell barrier function disorder is ulcerative colitis.
7. The method of claim 1 , wherein the therapeutic protein comprises an amino acid sequence having at least about 95% sequence identity to the sequence set forth in SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:13 or SEQ ID NO:19.
8. The method of claim 1 , wherein the therapeutic protein comprises an amino acid sequence having at least about 97% sequence identity to the sequence set forth in SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:13 or SEQ ID NO:19.
9. The method of claim 1 , wherein the therapeutic protein comprises an amino acid sequence selected from the group consisting of: SEQ ID NO:1, SEQ ID NO:9, SEQ ID NO:13 and SEQ ID NO:19.
10. The method of claim 1 , wherein administering is to the: mouth, gastrointestinal lumen, and/or intestines of the patient.
11. The method of claim 1 , wherein the patient experiences a reduction in at least one symptom associated with the gastrointestinal epithelial cell barrier function disorder.
12. The method of claim 1 , wherein the patient experiences a reduction in at least one symptom associated with the gastrointestinal epithelial cell barrier function disorder selected from the group consisting of: abdominal pain, blood in stool, pus in stool, fever, weight loss, frequent diarrhea, fatigue, reduced appetite, tenesmus, and rectal bleeding.
13. The method of claim 1 , wherein administering reduces one or more of: gastrointestinal inflammation in the patient, and intestinal mucosal inflammation in the patient.
14. The method of claim 1 , wherein administering increases one or more of: the production of mucin in intestinal tissue in the patient, and intestinal epithelium wound healing in the patient.
15. The method of claim 1 , further comprising: administering at least one second therapeutic agent to the patient.
16. The method of claim 1 , further comprising: administering at least one second therapeutic agent to the patient, said second therapeutic agent selected from the group consisting of: an anti-diarrheal, a 5-aminosalicylic acid compound, an anti-inflammatory agent, an antibiotic, an antibody, an anti-cytokine agent, an anti-inflammatory cytokine agent, a steroid, a corticosteroid, and an immunosuppressant.