Protein activity modification

• US 8,352,031 B2
• Filed: 05/24/2007
• Issued: 01/08/2013
• Est. Priority Date: 03/10/2004
• Status: Active Grant

• Current Assignee: Impulse Dynamics NV
• Original Assignee: Impulse Dynamics NV
• Inventors: Rousso, Benny, Sabbah, Hani N.
• Primary Examiner(s): Heller, Tammie K
• Application Number:
  US11/802,685
• Publication Number:
  US 20070293901A1
• Time in Patent Office: 2,056 Days
• Field of Search: 607/9, 607/22
• US Class Current: 607/22
• CPC Class Codes: A61N 1/3621 for treating or preventing abnormally high heart rate
• CPC Class Codes: A61N 1/3627 for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy

Abstract

A method of treating a cardiac arrhythmia, comprising: determining a desired arrhythmia control; selecting an electric field having an expected effect of modifying protein activity of at least one protein as a response of a cardiac tissue to the field, said expected effect correlated with said desired arrhythmia control; and applying said field to said cardiac tissue.

Claims

1. A method of treating a cardiac arrhythmia, comprising:

determining a desired arrhythmia control;

selecting an electric field having an expected effect of modifying protein activity of at least one protein as a response of a cardiac tissue to the field, said expected effect correlated with said desired arrhythmia control; and

applying said field to said cardiac tissue,

wherein said modification comprises phosphorylation of the at least one protein associated with arrhythmia as a direct effect of said field, thereby reducing a likelihood of a future arrhythmia.

2. A method according to claim 1, wherein the arrhythmia control is configured for at least one effect selected from the group consisting of treatment of a disease, a short term modification of tissue behavior, a long term modification of tissue behavior, an assessment of tissue state and an assessment of tissue response to stimulation.

3. A method according to claim 1, wherein the at least one protein comprises at least one GAP junction protein.

4. A method according to claim 3, wherein the at least one GAP junction protein comprises at least one Connexin protein.

5. A method according to claim 1, wherein the at least one protein comprises at least one intracellular calcium cycling protein.

6. A method according to claim 5, wherein the intracellular calcium cycling protein comprises at least one sarcoplasmic reticulum ATPase.

7. A method according to claim 5, wherein modifying protein activity further comprises modifying mRNA expression level.

8. A method according to claim 5, wherein the cardiac arrhythmia comprises a ventricular arrhythmia.

9. A method according to claim 5, wherein the cardiac arrhythmia comprises an atrial arrhythmia.

10. A method according to claim 9, wherein the atrial arrhythmia comprises atrial fibrillation.

11. A method according to claim 1, wherein the at least one protein comprises at least one zinc transporter gene.

12. A method according to claim 11, wherein the at least one zinc transporter gene comprises ZnT-1.

13. The method of claim 1, wherein the field is applied to diseased cardiac cells in a heart in which the diseased cardiac cells formed.

14. The method of claim 1, wherein the field includes a non-excitatory signal or signal component which causes at least part of said modifying the protein activity.

15. The method of claim 1, wherein applying comprises applying said field at a voltage of between 3 and 15 volts.

16. The method of claim 15, wherein applying comprises applying said field, at a delay of between 20 and 100 milliseconds from an activation at a location of said applying.

17. The method of claim 16, wherein applying comprises applying said field, with a duration of between 10 and 50 milliseconds.

18. The method of claim 17, wherein applying comprises applying said field to the right side of a ventricular septum.

19. The method of claim 18, wherein applying comprises applying said field for between 1 and 5 hours a day using an implantable stimulator.

20. The method of claim 16, wherein applying comprises applying said field, with a duration of between 20 and 40 milliseconds.

21. The method of claim 15, wherein applying comprises applying said field, at a delay of between 20 and 100 milliseconds from a pacing event.

22. The method of claim 1, wherein applying comprises applying said field for between 1 and 5 hours during a period of a day including at least one break period in said applying.

23. The method of claim 1, wherein applying comprises applying said field for between 5 and 12 hours during a period of a day including at least one break period in said applying.

24. The method of claim 1, wherein applying comprises applying said field as a series of at least four phases with delays therebetween.

25. The method of claim 1, wherein said applying comprises affecting a phosphorylation site on a protein as a direct effect of said field, in a cumulative manner.

26. A method according to claim 1, comprising applying said electric field for between 10% and 50% of beats in a day.

27. A method according to claim 1, wherein applying comprises applying a plurality of fields, one for each of a plurality of different chambers of a heart.

28. A method according to claim 1, wherein said field is a pro-arrhythmic field.

29. A method according to claim 1, wherein said phosphorylation is measurable within less than one minute from said application.

30. Apparatus for treating a cardiac arrhythmia, comprising:

at least one electrode adapted to apply an electric field to a cardiac tissue;

a controller including a memory having stored therein at least one electric field sequence which modifies protein activity in said cardiac tissue, said controller being configured to determine that a modification of said protein activity is desired as a means of an arrhythmia control and apply said sequence in response said determination to effect said arrhythmia control

wherein said modification comprises phosphorylation of a protein associated with arrhythmia as a direct effect of said field, thereby reducing a likelihood of a future arrhythmia.

31. Apparatus according to claim 30, wherein said sequence is operative to modify protein activity in diseased cardiac tissue.

32. Apparatus according to claim 30, wherein the field includes a non-excitatory signal or signal component which causes at least part of said modifying the protein activity.