Implantation of biological pacemaker that is molecularly determined

• US 20020187948A1
• Filed: 06/06/2001
• Published: 12/12/2002
• Est. Priority Date: 06/06/2001
• Status: Active Grant

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University), The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York)
• Inventors: Cohen, Ira S., Rosen, Michael R., Robinson, Richard B., Yu, Han-Gang
• Granted Patent: US 6,849,611 B2
• Time in Patent Office: Days
• US Class Current: 514/44
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/005 characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/06 Antiarrhythmics
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/10343 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2800/30 Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

Abstract

This invention provides for a method of inducing a current in the heart in a subject which comprises contacting a cell of the heart of a subject with a compound in a sufficient amount to induce a current in the cell of the heart of a subject. This invention also provides a method of treating a cardiac condition in a subject which comprises contacting a cell of the heart of the subject with a compound in an amount sufficient to increase the current expression of the cell, thereby treating the cardiac condition in the subject.

Claims

1. A method of treating a cardiac condition in a subject which comprises contacting a cell of the heart of the subject with a compound in an amount sufficient to increase the current expression of the cell, thereby treating the cardiac condition in the subject.

2. The method of claim 1, wherein the current is the pacemaker current.

3. The method of claim 1, wherein the subject is a mammal.

4. The method of claim 3, wherein the mammal is a human.

5. The method of claim 1, wherein the cell is a cardiac myocyte.

6. The method of claim 1, wherein the cardiac condition is a cardiac rhythm disorder.

7. The method of claim 6, wherein the cardiac rhythm disorder is selected from a group consisting of conductive block, complete atrioventricular block, incomplete atrioventricular block and sinus node dysfunction.

8. The method of claim 1, wherein the compound comprises a nucleic acid which encodes MiRP1.

9. The method of claim 1, wherein the compound comprises a nucleic acid which encodes an HCN channel.

10. The method of claim 9, wherein the HCN channel is HCN1.

11. The method of claim 9, wherein the HCN channel is HCN2.

12. The method of claim 9, wherein the HCN channel is HCN4.

13. The method of claim 1, wherein the compound comprises nucleic acids which encodes MiRP1 and a HCN channel.

14. The method of claim 13 wherein the HCN channel is HCN1.

15. The method of claim 13 wherein the HCN channel is HCN2.

16. The method of claim 13 wherein the HCN channel is HCN4.

17. The method of claim 1, wherein the step of contacting is selected from the group consisting of topical application, systemic administration to the subject, injection, electroporation, liposome application, viral-mediated contact, contacting the cell with the nucleic acid, and coculturing the cell with the nucleic acid.

18. The method of claim 17, wherein the administration of the contacting is selected from the group comprising topical administration, adenovirus infection, viral-mediated infection, liposome-mediated transfer, topical application to the cells of the subject, microinjection, and catheterization.

19. A method of inducing a current in the heart in a subject which comprises contacting a cell of the heart of a subject with a compound in a sufficient amount to induce a current in the cell of the heart of a subject, thereby inducing a current in the cell of the heart of the subject.

20. A method of increasing the heart rate in a subject which comprises contacting a cell of the heart of a subject with a compound in an amount sufficient to decrease the time constant of activation and deactivation of the cell of the heart, thereby increasing the heart rate in the subject.

21. A method of inducing a current in a cell which comprises contacting a cell with a compound in a sufficient amount to induce a current in the cell, thereby inducing a current in the cell.

22. A method of causing a contraction of a cell which comprises contacting the cell with a compound in an amount sufficient to induce a current required to cause a contraction of the cell, thereby causing a contraction of the cell.

23. A method of shortening the time required to activate and deactivate a cell which comprises contacting a cell with a compound in a sufficient amount to decrease the time constant of activation and deactivation of the cell, thereby shortening the time required to activate and deactivate the cell.

24. A method of changing the membrane potential of a cell which comprises contacting a cell with a compound in a sufficient amount to change the membrane potential of the cell, thereby changing the membrane potential of the cell.