Method for identifying substances which positively influence inflammatory conditions

• US 20030103965A1
• Filed: 08/05/2002
• Published: 06/05/2003
• Est. Priority Date: 08/06/2001
• Status: Abandoned Application

• Current Assignee: Boehringer Ingelheim Pharmaceuticals Incorporated (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Kraut, Norbert, Jung, Birgit, Mueller, Stefan
• Application Number:
  US10/211,239
• Publication Number:
  US 20030103965A1
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: G01N 33/6875 Nucleoproteins
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The present invention relates to NHR-proteins involved in inflammatory processes and the modulation of the function of such NHR-protein in order to positively influence inflammatory diseases.

Claims

1. A method for determining whether a substance is an activator or an inhibitor of a function of a NHR-protein deregulated in a hyperactivated macrophage, characterized in that the method comprises contacting the NHR-protein or variant, mutant or fragment thereof having a NHR-protein function with a substance to be tested whether it is an inhibitor or activator of a desired function of the NHR-protein, and measuring whether the desired function is inhibited or activated.

2. A method according to claim 1 in which the inhibition or activation of the desired function is measured directly.

3. A method according to claim 1 in which the inhibition or activation of the desired function is measured indirectly.

4. A method according to claim 1 in which the NHR-protein is a mammalian NHR-protein.

5. A method according to claim 4 in which the NHR-protein is a human NHR-protein.

6. A method according to claim 1 in which the analysis is performed using a cellular system.

7. A method according to claim 1 in which the analysis is performed using a cell-free system.

8. A method according to claim 1 in which said NHR-protein is selected from the group consisting of ERRα

(SEQ ID NO;

1); and

NR4 μ

l (SEQ ID NO;

2).

9. A method according to claim 8 in which ERRα

(SEQ ID NO;

1) is used or a variant, mutant or fragment thereof having the same function.

10. A method according to claim 8 in which NR4A1 (SEQ ID NO:

2) is used or a variant, mutant or fragment thereof having the same function.

11. A method according to claim 1 in which the function is DNA recognition and or DNA binding.

12. A method according to claim 1 in which the function is protein recognition and or protein binding.

13. A method for determining an expression level of a NHR-protein deregulated in a hyperactivated macrophage comprising determining the expression level of NHR-protein expressed in a macrophage.

14. A method according to claim 13 in which said macrophage is a mammalian macrophage.

15. A method according to claim 14 in which said macrophage is a human macrophage.

16. A method according to claim 13 in which said NHR-protein is selected from the group consisting of ERRα

(SEQ ID NO;

1); and

NR4A1 (SEQ ID NO;

2).

17. A method according to claim 13 or 16 in which said expression level is determined by determining the level of nucleic acid coding for a NHR-protein in a macrophage.

18. A method according to claim 13 or 16 in which said expression level is determined by determining the level of a NHR-protein.

19. A method according to anyone of claims 13-18 for diagnosis or monitoring of a chronic inflammatory airway disease.

20. A method according to claim 19 in which the chronic inflammatory airway disease is selected from the group consisting of chronic bronchitis and COPD.

21. A method according to claim 13 in which the analysis is performed using a macrophage or a part thereof obtainable from the site of inflammation.

22. A test system for determining whether a substance is an activator or an inhibitor of a function a NHR-protein deregulated in a hyperactivated macrophage comprising al least a NHR-protein or a variant, or a mutant, or a fragment thereof having a NHR-protein function.

23. A test system according to claim 22 in which said NHR-protein is selected from the group consisting of ERRα

(SEQ ID NO;

1); and

NR4A1 (SEQ ID NO;

2).

24. A test system according to claim 23 comprising a cell expressing a NHR-protein.

25. A substance determined to be an activator or inhibitor of a NHR-protein deregulated in a hyperactivated macrophage.

26. A substance which is an activator or inhibitor of a NHR-protein deregulated in a hyperactivated macrophage for the treatment for a disease.

27. A substance according to claim 26 in which said disease is a chronic inflammatory airway disease.

28. A substance according to claim 27 in which said chronic inflammatory airway disease is selected from the group consisting of chronic bronchitis and COPD.

29. A pharmaceutical composition comprising at least one substance determined to be an activator or inhibitor of a NHR-protein deregulated in a hyperactivated macrophage.

30. Use of a substance determined to be an activator or inhibitor of a NHR-protein for preparing a pharmaceutical composition for treating a chronic inflammatory airway disease.

31. Use of a substance according to claim 30 in which the chronic inflammatory airway disease is selected from the group consisting of chronic bronchitis and COPD.

32. A method for treating a chronic inflammatory airway disease which method comprises administering to a being in need of such treatment a suitable amount of a pharmaceutical composition comprising at least one substance determined to be an activator or inhibitor of a NHR-protein.

33. A method according to claim 32 for treating a mammal.

34. A method according to claim 32 for treating a human being.

35. A method according to claim 32 for treating a chronic inflammatory airway disease selected from the group consisting of chronic bronchitis and COPD.

36. A method for selectively modulating a NHR-protein in a macrophage, comprising administering a substance determined to be an activator or inhibitor of a NHR-protein.

37. A method according to claim 36 in which the macrophage is involved in a chronic inflammatory airway disease.

38. A method according to claim 37 in which the chronic inflammatory airway disease is selected from the group consisting of chronic bronchitis and COPD.