Methods for treating restenosis using annexin a5

Abstract

A method for the prophylaxis or treatment of restenosis comprising administering a therapeutically effective amount of Annexin A5 or a functional analogue or variant thereof to a patient in need of such treatment. A method for the treatment of stenosis in a patient comprising performing an intervention for the treatment of stenosis in conjunction with administering a therapeutically effective amount of Annexin A5 or a functional analogue or variant thereof. A pharmaceutical composition comprising a therapeutically effective amount of Annexin A5 or a functional analogue or variant thereof for the prophylaxis or treatment of restenosis. A drug eluting stent, wherein the drug is Annexin A5 or a functional analogue or variant thereof, and a method of making such a stent.

What is claimed: 
     
         1 . A method of treating or reduction in the development of vascular inflammation in a subject comprising administering to said subject a therapeutically effective amount of Annexin A5 or a functional analog or variant thereof. 
     
     
         2 . The method of  claim 1 , wherein said Annexin A5 or functional analog or variant thereof reduces or prevents of the activation of inflammatory cells in the vascular endothelium. 
     
     
         3 . The method of  claim 1 , wherein said Annexin A5 or functional analog or variant thereof reduces the accumulation of leukocytes in the vascular endothelium. 
     
     
         4 . The method of  claim 1 , wherein the vascular inflammation is provoked by an intervention for the treatment of stenosis. 
     
     
         5 . The method of  claim 4 , wherein the intervention for the treatment of stenosis is a surgical intervention. 
     
     
         6 . The method of  claim 4 , wherein the intervention for the treatment of stenosis is a catheter-based intervention. 
     
     
         7 . The method of  claim 1 , wherein the therapeutically effective amount of Annexin A5 or a functional analogue or variant thereof is administered parenterally, intravenously, intra-arterially, intra-peritoneally, intra-muscularly, subcutaneously or is administered locally from a drug eluting stent. 
     
     
         8 . The method of  claim 1 , wherein the Annexin A5 or the functional analogue or variant thereof is administered in conjunction with a thrombolytic therapeutic. 
     
     
         9 . The method of  claim 1 , wherein the Annexin A5 or the functional analogue or variant thereof is selected from the group consisting of:
 a) human Annexin A5 (SEQ ID NO:1);   b) a mammalian orthologue of human Annexin A5;   an allelic or genetic variant of a) or b);   d) a functional analogue of Annexin which is a protein which is more than 50%, more than 75%, such as more than 80%, more than 90%, or even more preferably more than 95% identical to human Annexin A5, SEQ ID NO:1;   e) a dimer of, or fusion protein comprising, any of a), b), c) or d); and   f) a PEGylated variant of any of a), b), c), d) or e).   
     
     
         10 . The method of  claim 1 , wherein the Annexin A5 or the functional analogue or variant thereof is human recombinant Annexin A5. 
     
     
         11 . The method of  claim 5 , wherein the surgical intervention is bypass grafting. 
     
     
         12 . The method of  claim 6 , wherein the catheter-based intervention is balloon angioplasty with or without implantation of a stent, and with or without atherectomy. 
     
     
         13 . The method of  claim 8 , wherein the thrombolytic therapeutic is aspirin, clopidogrel, triclopidine, tissue plasminogen activator, urokinase, or a bacterial enzyme.