Reversing Intestinal Inflammation by Inhibiting Retinoic Acid Metabolism

• US 20130131129A1
• Filed: 08/22/2012
• Published: 05/23/2013
• Est. Priority Date: 08/23/2011
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Leong, Hwei Xian, Engleman, Edgar G.
• Granted Patent: US 9,248,120 B2
• Time in Patent Office: Days
• US Class Current: 514/367
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031

Abstract

An agent that increases local concentration of retinoic acid (RA) in the intestine through modifying enzymatic pathways involved in RA metabolism is administered in a dose effective to inhibit or reverse production of inflammatory mediators by intestinal dendritic cells and thereby reduce intestinal inflammation and tumor growth associated with intestinal inflammation.

Claims

1. A method of reducing chronic intestinal inflammation in an individual, the method comprising:

administering to the individual an effective dose of an agent that increases local concentration of retinoic acid (RA) through modifying enzymatic pathways involved in RA metabolism, wherein inflammation is reduced.

2. The method of claim 1, wherein the dose is effective to maintain the tolerogenic functions of intestinal dendritic cells or neutralize a pre-existing inflammatory environment.

3. The method of claim 2, wherein the agent increases activity of retinaldehyde dehydrogenase or retinol dehydrogenase in intestinal tissues.

4. The method of claim 2, wherein the agent inhibits activity of CYP26A1.

5. The method of claim 4, wherein the agent is Liarozole or Talarozole.

6. The method of claim 1, wherein the agent is orally administered.

7. The method of claim 1, wherein the individual is a human.

8. The method of claim 1, wherein the chronic intestinal inflammation predisposes the individual to colorectal cancer.

9. The method of claim 8, wherein the individual is diagnosed with FAP.

10. The method of claim 1, wherein the individual is diagnosed with IBD.

11. The method of claim 1, wherein the individual is diagnosed with Crohn'"'"'s disease.

12. The method of claim 1, wherein the individual is diagnosed with Ulcerative Colitis.