Inflammatory bowel disease therapies
View Patent ↗The invention relates to methods of treating inflammatory bowel disease in a subject. Methods of promoting intestinal barrier function as well as related compositions are also provided.
1. A method for treating inflammatory bowel disease in a subject having or at risk of having inflammatory bowel disease, comprising
administering a therapeutically effective amount of an agent that inhibits HIF hydroxylase to the subject.
2. The method of claim 1 , wherein the inflammatory bowel disease is ulcerative colitis.
3. The method of claim 1 , wherein the inflammatory bowel disease is Crohn's disease.
4. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase is a HIF prolyl hydroxylase inhibitor.
5. The method of claim 4 , wherein the HIF prolyl hydroxylase is EGLN1, EGLN2, or EGLN3.
6. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase is a HIF asparaginyl hydroxylase inhibitor.
7. The method of claim 6 , wherein the HIF asparaginyl hydroxylase is FIH.
8. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase is a compound that inhibits 2-oxoglutarate dioxygenase enzyme activity.
9. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase is [(4-Hydroxy-7-phenylsulfanyl-isoquinoline-3-carbonyl)-amino]-acetic acid.
10. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase is a HIF hydroxylase expression inhibitor.
11. The method of claim 10 wherein the HIF hydroxylase expression inhibitor is small interfering nucleic acid.
12. The method of claim 10 , wherein the HIF hydroxylase expression inhibitor is a transgene that expresses a small interfering nucleic acid capable of inhibiting expression of a HIF hydroxylase gene.
13. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase selectively inhibits PHD-1.
14. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase selectively inhibits PHD-2.
15. The method of claim 1 , wherein the agent that inhibits HIF hydroxylase selectively inhibits PHD-3.
16. A method for reducing or ameliorating a symptom of inflammatory bowel disease in a subject, the method comprising administering a therapeutically effective amount of an agent that inhibits HIF hydroxylase to the subject.
17. The method of claim 16 , wherein the subject has ulcerative colitis.
18. The method of claim 16 , wherein the subject has Crohn's disease.
19. A method for reducing intestinal permeability in a subject having inflammatory bowel disease, the method comprising administering a therapeutically effective amount of an agent that inhibits HIF hydroxylase to the subject.
20. A method for improving intestinal barrier function in a subject having inflammatory bowel disease, the method comprising administering a therapeutically effective amount of an agent that inhibits HIF hydroxylase to the subject.