Methods for treating an inflammatory disease of the bowel

• US 7,998,474 B2
• Filed: 10/31/2002
• Issued: 08/16/2011
• Est. Priority Date: 11/21/2001
• Status: Expired due to Fees

• Current Assignee: Armistice Capital Master Fund Ltd. (Armistice Capital LLC)
• Original Assignee: The Rowett Research Institute (University of Aberdeen)
• Inventors: Kelly, Denise
• Primary Examiner(s): DUNSTON, JENNIFER ANN
• Application Number:
  US10/285,224
• Publication Number:
  US 20030133875A1
• Time in Patent Office: 3,211 Days
• Field of Search: 424/93.4, 424/184.1, 424/780
• US Class Current: 424/93.4
• CPC Class Codes: A61K 31/02 Halogenated hydrocarbons
• CPC Class Codes: A61K 35/74 Bacteria therapeutic use of a bacterial protein A61K38/00
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/10 Anti-acne agents
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: G01N 2333/4703 Regulators; Modulating activity
• CPC Class Codes: G01N 2500/00 Screening for compounds of potential therapeutic value
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6872 Intracellular protein regulatory factors and their receptors, e.g. including ion channels
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The invention relates to an assay to select a candidate drug for the treatment of inflammatory disease due to cytokine production. The assay comprises: a) exposing said candidate drug to intestinal cells; and b) analysing the effect of the said candidate drug selected from the group consisting of the variation of nuclear export or import of transcription factors from the NF-κB family the disruption of transcriptional activity of transcription factors from the NF-κB family, the differential histone acetylation of p65 (RelA); the variation of the amount of PPARγ/RelA complexes in the cytosol of the cells; and a combination thereof. The invention further relates to methods for the treatment of inflammatory cytokine production associated diseases and to the use of a therapeutically effective dose of Bacteroides thetaiotaomicron or a component thereof.

Claims

1. A method of treating inflammatory response of intestinal cells in a mammal afflicted with an inflammatory disease of the bowel, said inflammatory response being caused by NF-κ

B-induced inflammatory cytokines, said method comprising the step of administering to the subject a composition comprising as the only bacterial anti-inflammatory active ingredient a therapeutically effective dose of Bacteroides thetaiotaomicron.

2. The method of claim 1, wherein said Bacteroides thetaiotaomicron are administered live to the subject by means of a foodstuff or suppository.

3. The method of claim 1, wherein said inflammatory disease of the bowel is Crohn'"'"'s disease.

4. The method of claim 1, wherein the therapeutically effective dose of Bacteroides thetaiotaomicron is delivered orally.

5. The method of claim 1, wherein transcriptional activity of NF-κ

B is altered in the subject by enhanced nuclear export of the NF-κ

B.

6. The method of claim 1, wherein an amount of PPARγ

/RelA complexes in the cell cytosol of the subject is increased.

7. The method of claim 1, wherein said inflammatory response is determined through measurement of the levels of one or more cytokines selected from the group consisting of TNF-α

, IL-8, MIP-2α and

Cox-2.