METHODS OF TREATMENT AND NOVEL CONSTRUCTS
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.
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).