Methods of treatment and novel constructs

Abstract

The present invention provides novels method of targeting delivery of a compound to hypoxic cells, for example treatment of diseases and disorders associated with hypoxia, comprising administration of a construct comprising a targeting carrier peptide and a compound for delivery to a hypoxic cell. The invention also provides novel methods for the treatment of diseases or disorders of the eye by administration of a novel construct, a nucleic acid encoding a novel construct, and/or a nucleic acid vector comprising a nucleic acid encoding a novel construct. The invention further provides novel constructs, nucleic acids encoding such constructs, and/or nucleic acid vectors comprising nucleic acids encoding such constructs.

What is claimed is: 
     
         1 - 34 . (canceled) 
     
     
         35 . A method of treating acute ischemia in a subject comprising administering a therapeutically effect amount of a polypeptide construct comprising:
 (a) a targeting carrier peptide derived from the X-protein of the Hepatitis B virus and   (b) a peptide capable of interacting with an intracellular domain of connexin43 (Cx43).   
     
     
         36 . A method according to claim  1 , wherein the acute ischemia is a brain stroke, an acute ischemic stroke, a pulmonary embolism, a cardiovascular ischemia or a transient ischemic attack. 
     
     
         37 . A method according to claim  2 , wherein the cardiovascular ischemia is a heart attack, a myocardial infarction, a cardiac ischemia, pericarditis, or ischemic valve disease. 
     
     
         38 . A method according to claim  1 , wherein the targeting carrier peptide derived from the X-protein of the Hepatitis B virus is lclrpv (SEQ ID NO: 2). 
     
     
         39 . A method according to claim  1 , wherein the targeting carrier peptide derived from the X-protein of the Hepatitis B virus comprises or consists essentially of lclrpv (SEQ ID NO: 2). 
     
     
         40 . A method according to claim  1 , wherein the peptide capable of interacting with an intracellular domain of connexin43 is KQIEIKKFK (SEQ ID NO: 3). 
     
     
         41 . A method according to claim  1 , wherein the peptide capable of interacting with an intracellular domain of connexin43 comprises or consists essentially of KQIEIKKFK (SEQ ID NO: 3). 
     
     
         42 . A method according to claim  1 , wherein the peptide capable of interacting with an intracellular domain of connexin43 is lclrpvGGKQIEIKKFK (SEQ ID NO: 1). 
     
     
         43 . A method according to claim  1 , wherein the peptide capable of interacting with an intracellular domain of connexin43 comprises or consists essentially of lclrpvGGKQIEIKKFK (SEQ ID NO: 1). 
     
     
         44 . A method according to claim  2 , further comprising administration of a second compound comprising a therapeutically effect amount of an anticoagulant or a clot breakdown compound. 
     
     
         45 . A method according to claim  10 , wherein the second compound comprises a tissue plasminogen activator or a recombinant tissue plasminogen activator. 
     
     
         46 . A method according to claim  11 , wherein the tissue plasminogen activator is selected from the group consisting of alteplase, reteplase, tenecteplase and desmoteplase. 
     
     
         47 . A method according to claim  10 , wherein administration of the second compound occurs prior to reperfusion, during reperfusion and/or after reperfusion. 
     
     
         48 . A method of treating chronic ischemia in a subject comprising administering a therapeutically effect amount of a polypeptide construct comprising:
 (a) a targeting carrier peptide derived from the X-protein of the Hepatitis B virus and   (b) a peptide capable of interacting with an intracellular domain of connexin43 (Cx43).   
     
     
         49 . A method according to claim  14 , wherein the polypeptide construct comprises or consists essentially of lclrpvGGKQIEIKKFK (SEQ ID NO: 1). 
     
     
         50 . A method according to claim  1 , wherein the ischemia is a brain stroke, an acute ischemic stroke, a pulmonary embolism, a cardiovascular ischemia or a transient ischemic attack and the polypeptide construct comprises or consists essentially of lclrpvGGKQIEIKKFK (SEQ ID NO: 1).