Protein activity modification

• US 20090292324A1
• Filed: 12/09/2005
• Published: 11/26/2009
• Est. Priority Date: 03/10/2003
• Status: Active Grant

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Mika, Yuval, Rousso, Benny, Ben-Haim, Shlomo, Sabbah, Hani N.
• Granted Patent: US 9,931,503 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61N 1/205 for promoting a biological process
• CPC Class Codes: A61N 1/32 alternating or intermittent currents applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02
• CPC Class Codes: A61N 1/326 for promoting growth of cells, e.g. bone cells
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves

Abstract

A method of modifying tissue behavior, including cardiac tissue, comprising:

• • determining a desired modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation;
  • selecting an electric field having a known effect of modifying protein activation levels of at least one protein as an immediate response of a tissue to the field, said known effect correlated with said desired modification; and
  • applying said field to said tissue.

Claims

1. A method of modifying tissue behavior, comprising:

determining a desired modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation;

selecting an electric field having a known effect of modifying protein activation levels of at least one protein as an immediate response of a tissue to the field, said known effect correlated with said desired modification; and

applying said field to said tissue, wherein said tissue comprises cardiac tissue.

3. A method according to claim 1 wherein at least one of said at least one protein is an SR protein.

4. A method according to claim 1, wherein at least one of said at least one protein is not sensitive to physiologically occurring inter-cellular electric fields.

5. A method according to claim 1, wherein at least one of said at least one protein is not an ion transport protein.

7. A method according to claim 1, wherein said at least one protein comprises phospholamban.

10. A method according to claim 1, wherein said at least one protein comprises a plurality of proteins, wherein said plurality of proteins belong to at least 2 separate biochemical control pathways.

11. A method according to claim 1, wherein said at least one protein comprises a plurality of proteins, wherein said plurality of proteins belong to at least 3 separate biochemical control pathways.

18. A method according to claim 1, wherein modifying protein activation levels comprises modifying the activities of existing proteins, without synthesizing new proteins.

19. A method according to claim 1, wherein said immediate response comprises a response within less than 10 minutes.

20. A method according to claim 19, wherein said immediate response comprises a response within less than 2 minutes.

22. A method according to claim 19, wherein said immediate response comprises a response within less than 2 seconds.

24. A method according to claim 1, wherein said modifying is a transient modification temporally correlated with said applying.

25. A method according to claim 1, wherein said modifying is a persistent modification lasting at least 10 times the length of said applying.

27. A method according to claim 1, wherein said modifying comprises modifying a ratio between protein configurations of different activation levels of at least one of said at least one protein by a factor of at least 1.2.

28. A method according to claim 27, wherein said factor is at least 2.

30. A method according to claim 1, wherein determining a desired modification comprises determining a desired modification of tissue behavior.

31. A method according to claim 30, wherein said modification is a short term modification significant within 3 hours.

32. A method according to claim 30, wherein said modification is a long term modification significant within weeks.

33. A method according to claim 30, wherein said modification is a long term modification which comprises changes in protein expression levels.

34. A method according to claim 33, wherein said change is a change in at least 5 proteins associated with said behavior.

36. A method according to claim 1, wherein determining a desired modification of tissue behavior comprises determining said modification for treating a disease.

37. A method according to claim 36, wherein treating comprises increasing contractility.

38. A method according to claim 36, wherein treating comprises reversing a heart failure state in said tissue.

39. A method according to claim 38, wherein said reversing comprises reversing on a cellular level.

40. A method according to claim 36, wherein treating comprises normalizing protein expression levels.

41. A method according to claim 36, wherein treating comprises normalizing protein activity levels.

44. A method according to claim 36, wherein treating comprises modifying said treatment using a modification of protein activation levels as a target of said treating.

49. A method according to claim 1, wherein said assessing comprises assessing based on tissue biochemical markers.

50. A method according to claim 1, wherein assessing comprises classifying at least one of a disease state and disease severity.

58. A method according to claim 1, wherein said tissue comprises in-vivo tissue.

59. A method according to claim 1, wherein said tissue is selected from separated cells, broken down tissue in which cells are broken down, and tissue homogenate.

62. A method according to claim 1, wherein said determining a desired modification of tissue behavior comprises determining a modification for assessing a tissue response to stimulation.

63. A method according to claim 62, comprising modifying a selected field according to a response of said tissue to said applying.

64. A method according to claim 63, wherein said modifying a selected field comprises improving said field with respect to a desired effect of said field on said tissue.

67. A method according to claim 63, comprising measuring a non-immediate response of said tissue to said field.

68. A method according to claim 63, comprising measuring a non-local effect on remote tissue physiologically associated with said tissue in response to said field.

69. A method according to claim 1, wherein said field is non-excitatory for said tissue.

70. A method according to claim 1, wherein said tissue is contractile tissue and wherein said field reduces contraction of said tissue.

71. A method according to claim 1, wherein applying comprises applying said field in conjunction with a pharmaceutical, which has an interaction with an effect of said field on said tissue.

2. (canceled)

6. (canceled)

8-9. -9. (canceled)

12-17. -17. (canceled)

21. (canceled)

23. (canceled)

26. (canceled)

29. (canceled)

35. (canceled)

42-43. -43. (canceled)

45-48. -48. (canceled)

51-57. -57. (canceled)

60-61. -61. (canceled)

65-66. -66. (canceled)

72. Apparatus for treating tissue, comprising:

at least one electrode adapted to apply a field to in-vivo tissue;

a controller including a memory having stored therein at least one electric field sequence which modifies protein activity levels in said tissue, said controller being configured to determine that a modification of said protein activity is desired and apply said sequence in response said determination.

73-90. -90. (canceled)

91. A biochemical assaying kit, comprising:

an indicator of protein phosphorylation.

at least one electrode adapted to apply an electric field to a sample being tested with said kit; and

instructions for using said phosphorylation as an indicator of tissue state.

92-154. -154. (canceled)