Methods of treating restenosis

• US 20050112101A1
• Filed: 09/03/2004
• Published: 05/26/2005
• Est. Priority Date: 09/03/2003
• Status: Active Grant

• Current Assignee: Institut National De La Sante Et De La Recherche Medicale (Inserm) (Allianz Global Investors GmbH), The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: General Hospital Corporation and Institut National de La Sante et de La Recherche Medicale
• Inventors: Hajjar, Roger J., Del Monte, Federica, Lompr, Anne-Marie, Lipskaia, Larissa
• Granted Patent: US 7,291,604 B2
• Time in Patent Office: Days
• US Class Current: 424/93.200
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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: A61L 33/128 Other specific proteins or polypeptides not covered by A61L33/122 - A61L33/126
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 9/14 Hydrolases (3)
• CPC Class Codes: C12Y 306/03008 Ca2+-transporting ATPase (3.6.3.8)

Abstract

Restenosis in a subject can be treated by administering to a tissue, e.g., a blood vessel, of the subject an agent that increases SERCA activity. For example, a stent that is coated with the agent can be introduced into a blood vessel.

Claims

1. A method of treating restenosis, the method comprising:

identifying a subject in need of treatment, or at risk, for restenosis; and

administering a nucleic acid that encodes a SERCA polypeptide in a blood vessel of the subject.

2. The method of claim 1, wherein the SERCA polypeptide is SERCA1a, SERCA1b, SERCA2a, SERCA2b or SERCA3 polypeptide.

3. The method of claim 1, wherein the subject has undergone, is undergoing, or will undergo, percutaneous coronary intervention.

4. The method of claim 1, wherein the subject has undergone, is undergoing, or will undergo, angioplasty or balloon angioplasty.

5. The method of claim 1, wherein the subject has undergone, is undergoing, or will undergo insertion of a stent.

6. The method of claim 1, wherein the subject has undergone, is undergoing, or will undergo, insertion of a prosthesis, insertion of a graft, insertion of a stent, catheterization, or arterial blockage evaluation.

7. The method of claim 1, wherein the method comprises implanting in the vessel a stent coated with or containing the agent.

8. The method of claim 1, wherein the agent is packaged in a viral particle.

9. The method of claim 8, wherein the SERCA nucleic acid is a component of an adenovirus-based, adeno-associated virus-based, lentivirus-based or plasmid-based vector.

10. The method of claim 9, wherein the vector compromises the nucleic acid encoding SERCA operably linked to a viral or cardiac specific promoter.

11. The method of claim 9, wherein the vector compromises the nucleic acid encoding SERCA operably linked to an inducible promoter.

12. The method of claim 1, wherein the agent is administered in an amount effective to prevent neointimal hyperplasia.

13. A method of treating restenosis, the method comprising:

identifying a subject having or at risk of having a restenotic vessel; and

implanting in the vessel a stent coated with or containing a nucleic acid that encodes SERCA2a.

14. The method of claim 13 wherein the stent is coated with viral particles that include the nucleic acid that encodes SERCA.

15. A method of treating a cardiovascular disorder, the method comprising:

implanting a stent that is coated with or containing a nucleic acid that encodes SERCA in a blood vessel of a subject.

16. The method of claim 15 wherein the stent is coated with viral particles that include the nucleic acid that encodes SERCA.

17. A method of treating a cardiovascular disorder, the method comprising:

introducing a nucleic acid that encodes SERCA into cells of a blood vessel; and

implanting a stent in the blood vessel.

18. The method of claim 17 wherein the nucleic acid is introduced into the cells before the stent is implanted.

19. The method of claim 17 wherein the nucleic acid is introduced into the cell concurrent with implanting the stent.

20. The method of claim 17 wherein the nucleic acid is introduced into the cells after the stent is implanted.

21. A stent coated with or containing an agent, the agent comprising a nucleic acid that encodes a SERCA protein.

22. The stent of claim 21, wherein the agent is a nucleic acid that encodes SERCA2a.

23. The stent of claim 21, wherein the agent is packaged in a viral particle.

24. A kit comprising a stent coated with, or containing, an agent comprising a nucleic acid that encodes a SERCA protein, and instructions for using the stent to treat restenosis.

25. The kit of claim 24, wherein the agent is a SERCA2a encoding nucleic acid.