Protein activity modification

• US 10,352,948 B2
• Filed: 08/29/2016
• Issued: 07/16/2019
• 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:
  US15/249,506
• Publication Number:
  US 20160370384A1
• Time in Patent Office: 1,051 Days
• 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 for classifying a patient according to an expected responsiveness to a non-excitatory electric field treatment using an extracted heart tissue sample, comprising:

applying a non-excitatory electric field to an extracted heart tissue sample;

testing expression markers of a plurality of proteins in said tissue sample, after said applying, to obtain results of said testing, at least one of said plurality of proteins being an HF-related protein; and

classifying the suitability of said patient for a non-excitatory electric field treatment based on said results for a plurality of proteins expression markers.

2. The method according to claim 1, wherein said non-excitatory electric field causes contractility modulation of said tissue sample.

3. The method according to claim 1, wherein said testing expression markers comprises determining a phosphorylation level of at least one protein of said plurality of proteins.

4. The method according to claim 3, further comprising determining pre-treatment levels of said phosphorylation level.

5. The method according to claim 1, wherein said tissue sample originates from a left ventricle of said patient'"'"'s heart.

6. The method according to claim 1, wherein said plurality of proteins comprise a plurality of HF-related proteins.

7. The method according to claim 1, further comprising pre-testing said plurality of protein expression markers prior to said applying an electric field.

8. The method according to claim 1, wherein said applying comprises a scheme of a plurality of contractility modulating electric fields.

9. The method according to claim 8, further comprising storing said protein expression results for each of said plurality of electrification schemes.

10. The method according to claim 1, further comprising selecting a part of the tested sample and applying a test thereto.

11. The method according to claim 1, wherein said testing expression markers comprises determining protein expression levels.

12. The method according to claim 1, wherein said testing expression markers comprises determining mRNA expression levels.

13. The method according to claim 1, wherein said applying an electric field is conducted in conjunction with administering a medicament.

14. The method according to claim 1, further comprising homogenizing the tissue sample prior to applying said electric field.

15. A kit for classifying a patient according to an expected responsiveness to a non-excitatory electric field treatment using an extracted heart tissue sample, said kit comprising:

(a) a sample chamber configured for use outside the body;

(b) at least one electrode configured to apply an electric field to tissue within the sample chamber;

(c) a stimulator for applying to said electrode an electric field suitable for a non-excitatory stimulation of an extracted tissue sample within the sample chamber; and

(d) a plurality of indicators for a plurality of proteins expression markers, at least one of said plurality of proteins is an HF-related protein.

16. The kit according to claim 15, wherein said electric field is configured to cause contractility modulation of said tissue.

17. The kit according to claim 15, wherein said indicators comprise at least one indicator of protein phosphorylation.

18. The kit according to claim 15, further comprising instructions of use comprising at least one threshold of an expected value of said proteins expression markers.

19. The kit according to claim 15, wherein said stimulator is an implantable device.

20. The kit according to claim 15, further comprising a controller adapted to apply a scheme of a plurality of contractility modulating electric fields.

21. A method for determining the suitability of a treatment to a patient, according to an expected responsiveness to a non-excitatory electric field treatment using an extracted heart tissue sample, comprising:

applying a non-excitatory electric field to an extracted heart tissue sample;

testing expression markers of a plurality of proteins in said tissue sample, after said applying, to obtain results of said testing, at least one of said plurality of proteins being an HF-related protein; and

selecting a non-excitatory electric field treatment expected to have a therapeutic effect on said patient based on said results for a plurality of proteins expression markers.