Protein activity modification

• US 8,977,353 B2
• Filed: 08/20/2013
• Issued: 03/10/2015
• Est. Priority Date: 03/10/2004
• Status: Active Grant

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Rousso, Benny, Mika, Yuval, Ben-Haim, Shlomo, Sabbah, Hani N.
• Primary Examiner(s): VOORHEES, CATHERINE M
• Application Number:
  US13/970,647
• Publication Number:
  US 20130338425A1
• Time in Patent Office: 567 Days
• Field of Search: 607 2- 5, 607/9, 607 39- 59, 607/62, 600 9- 15
• US Class Current: 607/3
• 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 1/3627 for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy
• CPC Class Codes: A61N 1/3628 using sub-threshold or non-excitatory signals
• CPC Class Codes: A61N 1/3629 in combination with non-electric therapy
• CPC Class Codes: A61N 2/004 specially adapted for a specific therapy
• CPC Class Codes: C12N 13/00 Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/112 Disease subtyping, staging or classification
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

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 an expected effect of modifying protein activity of at least one protein as an immediate response of a tissue to the field, said expected effect correlated with said desired modification; and
  • applying said field to said tissue.

Claims

1. A method of modifying cardiac tissue behavior at a first location by application of an electric field to cardiac tissue at a second location, comprising:

determining a desired non-acute modification of protein activity and/or gene activity of cardiac tissue at said first location;

selecting electric field parameters including one or more of the second location, the duration of application of the field and the power level of the field having an expected effect of producing said desired non-acute modification of said protein activity and/or gene activity at said first location, but without causing a significant acute effect at the first location;

applying an electric field having the selected parameters to cardiac tissue at said second location to produce said selected non-acute modification at the first location, wherein said first location is sufficiently remote from said second location that a significant acute effect at the first location does not occur.

2. A method according to claim 1, wherein said modification comprises changing a gene program.

3. A method according to claim 2, wherein said gene program comprises a fetal gene program.

4. A method according to claim 1, wherein said modification comprises changing a protein activity profile.

5. A method according to claim 1, wherein the effect of said electric field is allowed to propagate from said second location to said first location by non-mechanical action.

6. A method according to claim 1, wherein the effect of said electric field is allowed to propagate from said second location to said first location in a manner other than by the nervous system.

7. A method according to claim 1, wherein the effect of said electric field is allowed to propagate from said second location to said first location by chemical action.

8. A method according to claim 1, wherein application of said electric field has substantially no long term effect at said second location.

9. A method according to claim 1, wherein application of said electric field has a long term effect at said second location.

10. A method according to claim 1, wherein application of said electric field has an immediate effect at an area of said second location.

11. A method according to claim 1, wherein application of said electric field has an effect on at least one of protein activity and gene activity at said second location.

12. A method according to claim 1, wherein said first and second locations include cardiac muscle.

13. A method according to claim 1, wherein said first location is affected to produce said modification within 3 months.

14. A method according to claim 1, wherein said second location is selected according to an expected amount of oxygenation thereat.

15. A method according to claim 1, comprising selecting said second location according to expected diffusion pathways between said first and second locations.

16. A method according to claim 10, wherein the area of said second location which is immediately affected by said application is smaller than 10 cm².

17. A method according to claim 1, wherein said electric field is applied in a chronic manner.

18. A method according to claim 1, wherein applying said electric field increases contractility at said second location.

19. A method according to claim 1, wherein applying said electric field does not increase oxygen usage at said second location.

20. A method according to claim 1, wherein said electrical field is a non-excitatory field.

21. A method according to claim 1, wherein said electrical field reduces contraction at said second location.

22. A method according to claim 1, further comprising modifying said electric field responsive to an effect of said field.

23. A method according to claim 1, wherein said second location is at a cardiac septum and said first location is not.

24. A method according to claim 1, wherein said applying comprises improving a clinical condition of a heart failure patient by said applying.

25. A method according to claim 10, wherein the area of said second location which is immediately affected by said application is in the range of about 1 to about 20 cm².

26. A method according to claim 1, wherein a time scale for an effect on protein activity at the first location by application of the electric field at the second location is within the range of about 1 to about 3 days.

27. A method according to claim 1, wherein the effect on gene activity is a change in mRNA transcription and a time scale for said effect on mRNA transcription at the first location by a application of the electric field at the second location is in the range of about 1 to about 4 hours.

28. A method according to claim 1, wherein application of the electric field at the second location produces no acute effects noticeable at the first location over time scales in the range of about 1 to about 20 minutes.

29. A method according to claim 1, wherein application of the electric field at the second location produces no acute effects noticeable at the first location over time scales in the range of about 1 to about 20 hours.

30. A method according to claim 1, wherein the effect on protein activity is a change in formation of protein, and a time scale for said effect on formation of protein at the first location by application of the electric field at the second location is within about 3 weeks.