EVALUATING AND TREATING SCLERODERMA

• US 20090220488A1
• Filed: 08/24/2006
• Published: 09/03/2009
• Est. Priority Date: 08/31/2005
• Status: Abandoned Application

• Current Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Original Assignee: Biogen Idec MA Inc. (Biogen, Inc.)
• Inventors: Gardner, Humphrey
• Application Number:
  US12/065,217
• Publication Number:
  US 20090220488A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

The expression of a number of genes is altered in scleroderma. Therapeutic methods for treating scleroderma can include counteracting the effects of the altered gene expression profile. Further, scleroderma can be diagnosed and monitored by evaluating the expression of one or more of the altered genes.

Claims

1. A method of treating or preventing scleroderma or other fibrotic disorder, the method comprising:

administering, to a subject, a Wnt signalling antagonist, in an amount effective to treat or prevent scleroderma.

2. The method of claim 1 wherein the Wnt signalling antagonist is an antagonist of canonical Wnt signalling.

3. The method of claim 1 wherein the Wnt signalling antagonist is an antagonist of non-canonical Wnt signalling.

4. The method of claim 1 wherein the Wnt signalling antagonist comprises a protein.

5. The method of claim 1 wherein the Wnt signalling antagonist is a Wnt binding protein.

6. The method of claim 5 wherein the Wnt signalling antagonist comprises a protein at least 90% identical to a naturally occurring Wnt-binding protein or a functional fragment thereof.

7. The method of claim 6 wherein the Wnt signalling antagonist comprises a Wnt-binding fragment of a naturally occurring Wnt-binding protein.

8. The method of claim 5 wherein the Wnt signalling antagonist comprises a protein at least 90% identical to a Wnt-binding fragment of an sFRP protein (soluble frizzled-related protein), WIF-1, or Cerberus.

9. The method of claim 8 wherein the Wnt signalling antagonist comprises a Wnt-binding fragment of an sFRP protein (soluble frizzled-related protein), WIF-1, or Cerberus.

10. The method of claim 5 wherein the Wnt signalling antagonist comprises a protein at least 90% identical to a Wnt-binding fragment of a Dickkopf protein.

11. The method of claim 10 wherein the Wnt signalling antagonist comprises a Wnt-binding fragment of a Dickkopf protein.

12. The method of claim 5 wherein the Wnt signalling antagonist comprises an antibody that binds to Wnt.

13. The method of claim 1 wherein the Wnt signalling antagonist comprises an agent that inhibits interaction between a canonical Wnt and Frizzled or LRP5/6.

14. The method of claim 13 wherein the Wnt signalling antagonist comprises an antibody that binds to Frizzled or LRP5/6.

15. The method of claim 1 wherein the subject is a human.

16. The method of claim 15 wherein the subject is a human diagnosed with scleroderma.

17. The method of claim 15 wherein the subject is a human who has been diagnosed as having decreased WIF1 expression in a skin biopsy.

18. A method of treating or preventing scleroderma, the method comprising:

administering, to a subject, an agent that comprises a functional fragment of WIF1, in an amount effective to treat or prevent scleroderma.

19. The method of claim 18 wherein the fragment is a Wnt-binding fragment of WIF1.

20. The method of claim 18 wherein the agent comprises full-length, mature WIF1.

21. A method of treating or preventing scleroderma, the method comprising:

administering, to a subject, an agent that increases activity or expression of WIF1 or an sFRP protein, in an amount effective to treat or prevent scleroderma.

22. A method of treating or preventing scleroderma, the method comprising:

administering, to a subject, a IGF binding agent, in an amount effective to treat or prevent scleroderma.

23. The method of claim 22 wherein the IGF binding agent binds to IGF-I or IGF-II.

24. The method of claim 22 wherein the IGF binding agent comprises IGF binding regions of a naturally occurring IGFBP.

25. The method of claim 22 wherein the IGFBP is IGFBP-3.

26. The method of claim 22 wherein the IGF binding agent comprises a full-length, mature IGFBP.

27. The method of claim 22 wherein the IGF binding agent comprises an antibody that binds to IGF-I or IGF-II.

28. A method of treating or preventing scleroderma, the method comprising:

administering, to a subject, an agent that (i) increases expression of a gene in Table 1, or (ii) increases activity of a gene product encoded by the gene, wherein the agent is administered in an amount effective to treat or prevent scleroderma.

29. The method of claim 28 wherein the agent is a nucleic acid that encodes a protein that comprises a functional fragment of the gene product.

30. The method of claim 29 wherein the nucleic acid is in a viral vector and delivered using viral particle.

31. The method of claim 29 wherein the agent comprises a functional fragment of the gene product.

32. The method of claim 29 wherein the agent comprises the gene product.

33. A method of treating or preventing scleroderma, the method comprising:

administering, to a subject, an agent that (i) decreases expression of a gene in Table 2, or (ii) decreases activity of a gene product encoded by the gene, wherein the agent is administered in an amount effective to treat or prevent scleroderma.

34. The method of claim 33 wherein the agent is a nucleic acid antagonist of gene expression.

35. The method of claim 34 wherein the nucleic acid antagonist is an RNAi.

36. The method of claim 34 wherein the agent is an antibody that binds to the gene product.

37. A method of evaluating a subject, the method comprising:

obtaining a sample from a subject; and

evaluating expression of WIF-1 in cells in the biopsy, wherein a decrease in WIF-1 expression relative to a reference is indicative of scleroderma or risk for scleroderma.

41. The method of claim 37 or 38 wherein the evaluating comprises a quantitative evaluation of expression levels.

42. The method of claim 37 or 38 wherein the evaluating comprises a qualitative evaluation of expression levels.

43. The method of claim 37 or 38 wherein the reference is a parameter obtained by evaluating a normal subject who does not have scleroderma.

44. The method of claim 37 or 38 wherein a plurality of genes are evaluated and the expression of each of the genes is compared to corresponding references.

45. The method of claim 37 or 38 wherein a plurality of genes are evaluated to obtain a profile of gene expression, and the profile is compared to a corresponding reference profile.

47. The method of claim 37, 38 or 46 wherein the sample comprises a skin biopsy.

48. The method of claim 37, 38 or 46 wherein the sample comprises a serum sample.

49. The method of claim 37, 38 or 46 further comprising, if the subject is indicated for scleroderma or risk for scleroderma, administering a therapy for scleroderma to the subject.

50. The method of claim 37, 38 or 46 further comprising preparing a report indicating a diagnosis of scleroderma or risk for scleroderma using results of the evaluating.

38. A method of evaluating a subject, the method comprising:

obtaining a sample from a subject; and

evaluating expression of a gene in Table 1 or 2 in cells in the biopsy, wherein an alteration in expression of the gene relative to a reference is indicative of scleroderma or risk for scleroderma.

39. The method of claim 38 wherein the gene is listed in Table 1 and a decrease in expression of the gene relative to a reference is indicative of scleroderma or risk for scleroderma.

40. The method of claim 38 wherein the gene is listed in Table 2 and an increase in expression of the gene relative to a reference is indicative of scleroderma or risk for scleroderma.

46. A method of evaluating a subject, the method comprising:

obtaining a sample from a subject; and

evaluating expression of a collagen in cells in the biopsy, wherein a increase in collagen expression relative to a reference is indicative of scleroderma or risk for scleroderma.

51. The method of claim 46 wherein the collagen is collagen XI.

52. A computer-readable database that comprises a plurality of records,

each record of the plurality comprising:

a) a first field that comprises information about skin pathology of a subject and;

b) a second field that comprises information about expression of a gene in Table 1 or 2 in cells from a skin biopsy obtained from the subject.

53. The database of claim 52 wherein each record of the plurality farther comprises a field that comprises information identifying the subject.

54. The database of claim 52 wherein each record of the plurality farther comprises fields, each additional field comprising information about expression of a gene in Table 1 or 2 such that each record includes information for a plurality of genes in Table 1 or 2.