Use of anti-amyloid agents for treating and typing pathogen infections

• US 20090156471A1
• Filed: 07/14/2005
• Published: 06/18/2009
• Est. Priority Date: 07/15/2004
• Status: Abandoned Application

• Current Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Original Assignee: Ramot at Tel Aviv University Limited (Tel Aviv University)
• Inventors: Cherny, Izhack, Gazit, Ehud
• Application Number:
  US11/632,410
• Publication Number:
  US 20090156471A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/357 having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/385 having two or more sulfur atoms in the same ring
• CPC Class Codes: A61K 31/39 having oxygen in the same ring
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 38/05 Dipeptides
• CPC Class Codes: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics

Abstract

A method of preventing or treating a pathogen infection in a subject is provided. The method comprising administering to a subject in need thereof a therapeutically effective amount of an anti amyloid agent, thereby treating or preventing the pathogen infection in the subject.

Claims

1. A method of preventing or treating a pathogen infection in a subject, the method comprising administering to a subject in need thereof a therapeutically effective amount of an anti amyloid agent, thereby treating or preventing the pathogen infection in the subject.

8. The method and use of claim 1, wherein said pathogen infection comprises a bacterial infection.

9. The method and use of claim 1, wherein said pathogen infection comprises a fungi infection.

10. The methods, use and medical device of claim 1, wherein said anti-amyloid agent is a proteinaceous agent.

11. The methods, use and medical device of claim 10, wherein said proteinaceous agent is a peptide agent.

12. The methods, use and medical device of claim 11, wherein said peptide agent comprises an amino acid sequence selected from the group consisting of SEQ ID NO:

9, 10 and 11.

13. The methods, use and medical device of claim 11, wherein said peptide agent comprises an amino acid sequence X-Y or Y-X, wherein X is an aromatic amino acid and Y is any amino acid other than glycine, the peptide being at least 2 and no more than 15 amino acids in length.

14. The methods, use and medical device of claim 12, wherein at least one amino acid of said amino acid sequence of the peptide is a D stereoisomer.

15. The methods, use and medical device of claim 12, wherein at least one amino acid of said amino acid sequence of the peptide is an L stereoisomer.

16. The methods, use and medical device of claim 12, wherein Y is a polar uncharged amino acid selected from the group consisting of serine, threonine, asparagine, glutamine and natural derivatives thereof.

17. The methods, use and medical device of any of claim 12, wherein Y is a β

-sheet breaker amino acid.

18. The methods, use and medical device of claim 17, wherein said β

-sheet breaker amino acid is a naturally occurring amino acid.

19. The methods, use and medical device of claim 18, wherein said naturally occurring amino acid is selected from the group consisting of proline, aspartic acid, glutamic acid, glycine, lysine and serine.

20. The methods, use and medical device of claim 17, wherein said β

-sheet breaker amino acid is a synthetic amino acid.

21. The methods, use and medical device of claim 20, wherein said synthetic amino acid is a Cα

-methylated amino acid.

22. The methods, use and medical device of claim 21, wherein said Cα

-methylated amino acid is α

-aminoisobutyric acid.

23. The methods, use and medical device of claim 11, wherein the peptide is a linear or cyclic peptide.

24. The methods, use and medical device of claim 12, wherein the peptide is two amino acids in length and Y is a β

-sheet breaker amino acid.

25. The methods, use and medical device of claim 12, wherein the peptide is 3 amino acids in length, whereas Y is an aromatic amino acid and an amino acid residue attached to said amino acid sequence X-Y or Y-X is a β

-sheet breaker amino acid.

26. The methods, use and medical device of claim 25, wherein said β

-sheet breaker amino acid is at a C-terminus of the peptide.

27. The methods, use and medical device of claim 12, wherein the peptide is at least 4 amino acids in length and includes at least two serine residues at a C-terminus thereof.

28. The methods, use and medical device of any of claim 12, wherein the peptide is at least 3 amino acids in length and includes a thiolated amino acid at an N-terminus thereof.

29. The methods, use and medical device of claim 12, wherein the peptide is at least 3 amino acids in length and whereas at least one of said amino acids of the peptide other than X-Y is a β

-sheet breaker amino acid.

30. The methods, use and medical device of claim 12, wherein the peptide is at least 3 amino acids in length and whereas at least one of said amino acids of the peptide is a positively charged amino acid and at least one of said amino acids of the peptide is a negatively charged amino acid.

31. The methods, use and medical device of claim 1, wherein said anti-amyloid agent is a non-proteinaceous agent.

32. The methods, use and medical device of claim 31, wherein said non-proteinaceous agent comprises a compound having the general Formula I:

33. The methods, use and medical device of claim 32, wherein:

X is carbon;

Y is R₁₃R₁₄C—

CR₁₅R₁₆; and

Z is oxygen.

34. The methods, use and medical device of claim 33, wherein:

R₉ is oxo; and

R₁₀ is absent.

35. The methods, use and medical device of claim 33, wherein at least one of R₁₃-R₁₆ is selected from the group consisting of alkoxyphenyl, thioalkoxyphenyl, aryloxyphenyl, thioaryloxyphenyl, carboxyphenyl, thiocarboxyphenyl, phenol, hydroxyphenol and dihydroxyphenol.

36. The methods, use and medical device of claim 35, wherein each of R₁ and R₃ is hydroxy.

37. The methods, use and medical device of claim 33, wherein at least one of R₁₃-R₁₆ is alkyl.

38. The methods, use and medical device of claim 32, wherein:

X is carbon;

Y is oxygen;

Z is carbon or sulfur; and

at least one of R₅ and R₆ is oxo.

39. The methods, use and medical device of claim 34, wherein at least one of R₉ and R₁₀ is selected from the group consisting of alkoxyphenyl, thioalkoxyphenyl, aryloxyphenyl, thioaryloxyphenyl, carboxyphenyl, thiocarboxyphenyl, phenol, hydroxyphenol and dihydroxyphenol.

40. The methods, use and medical device of claim 32, wherein said compound is selected from the group consisting of phenol red, dimethoxy phenol red, methoxy phenol red, diacetoxy phenol red, acetoxy phenol red, pyrocatechol violet, phenolphthaleine, catechin, epigallocatechin gallate, epicatechin gallate, epicatechin, epigallocatechin, eriodictyol, quercetin, procyanidin, hydroxyphenyl, tocopherol, and bromophenol red.

41. The methods, use and medical device of claim 31, wherein said non peptide agent comprises a compound having the general formula:

42. The methods, use and medical device of claim 41, wherein:

each of X and Y is carbon; and

Z is nitrogen.

43. The methods, use and medical device of claim 42, wherein said double bond is between X and Y.

44. The methods, use and medical device of claim 41, wherein at least one of R₁-R₁₀ comprises a hydroxy group.

45. The methods, use and medical device of claim 43, wherein at least one of R₁-R₁₀ comprises a hydroxy group.

46. The methods, use and medical device of claim 45, wherein at least one of R₁ and R₉ comprises a hydroxy group.

47. The methods, use and medical device of claim 45, wherein at least one of R₁ and R₉ is a hydroxy group.

48. The methods, use and medical device of claim 47, wherein each of R₂-R₅ and R₇ is hydrogen and R₆, R₈ and R₁₀ are absent.

49. The methods, use and medical device of claim 48, wherein R₁ is hydrogen and R₉ is a hydroxy group.

50. The methods, use and medical device of claim 48, wherein R₁ is a hydroxy group and R₉ is hydrogen.

51. The methods, use and medical device of claim 45, wherein at least one of R₁-R₁₀ is a hydroxyalkyl.

52. The methods, use and medical device of claim 51, wherein at least one of R₇ and R₉ is a hydroxyalkyl.

53. The methods, use and medical device of claim 52, wherein each of R₁-R₅ is hydrogen and R₆, R₈ and R₁₀ are absent.

54. The methods, use and medical device of claim 52, wherein said hydroxyalkyl is hydroxymethyl.

55. The methods, use and medical device of claim 54, wherein R₇ is hydrogen and R₉ is said hydroxymethyl.

56. The methods, use and medical device of claim 55, wherein each of R₁-R₅ is hydrogen and R₆, R₈ and R₁₀ are absent.

57. The methods, use and medical device of claim 52, wherein each of R₇ and R₉ is a hydroxyalkyl.

58. The methods, use and medical device of claim 10, wherein said non-proteinaceous agent is a non-steroidal anti-inflammatory drug.

59. The methods, use and medical device of claim 10, wherein said non-proteinaceous agent is selected from the group consisting of nicotine, acridine, acridine orange, methylene blue, congo red, thioflavin-T and tetracycline.

2. Use of an anti-amyloid agent for the manufacture of a medicament identified for preventing or treating a pathogen infection in a subject.

3. A method of typing a pathogen, the method comprising monitoring an alteration in growth and/or infectivity of the pathogen in the presence of an anti-amyloid agent, thereby typing the pathogen.

4. A method of identifying an anti-amyloid agent, the method comprising:

(a) contacting molecules with an amyloid forming pathogen; and

(b) identifying at least one molecule of said molecules capable of altering amyloid formation of said amyloid forming pathogen, thereby identifying the anti-amyloid agent.

5. A medical device comprising an anti-amyloid agent attached thereto.

6. The medical device of claim 5, wherein the medical device is an intracorporeal device.

7. The medical device of claim 5, wherein the medical device is an extracorporeal device.