COMBINATION THERAPIES USING CYCLOSPORINE AND AROMATIC CATIONIC PEPTIDES
The invention provides compositions and methods for preventing or treating an ischemia-reperfusion injury, such as occurs during acute myocardial infarction and organ transplant in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof, and one or more additional active agents such as cyclosporine.
1 .- 20 . (canceled)
21 . A method for treating ischemia and/or reperfusion injury in a subject in need thereof, the method comprising administering simultaneously, separately or sequentially an effective amount of (i) an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof, wherein the aromatic-cationic peptide is selected from the group consisting of: Tyr- D -Arg-Phe-Lys-NH 2 ; 2′,6′-Dmt- D -Arg-Phe-Lys-NH 2 ; Phe- D -Arg-Phe-Lys-NH 2 ; 2′,6′-Dmp- D -Arg-Phe-Lys-NH 2 ; and D -Arg-2′,6′-Dmt-Lys-Phe-NH 2 and (ii) an additional active agent comprising a functional analogue of cyclosporine, wherein the aromatic-cationic peptide is linked to the additional active agent by a linker.
22 . The method of claim 21 , wherein the pharmaceutically acceptable salt comprises acetate salt or trifluororacetate salt.
23 . The method of claim 21 , wherein the aromatic-cationic peptide comprises D-Arg-2′6′-Dmt-Lys-Phe-NH 2 or a pharmaceutically acceptable salt thereof selected from acetate salt or trifluororacetate salt.
24 . The method of claim 21 , wherein the linker comprises an enzyme-cleavable linker or a pH-sensitive linker.
25 . The method of claim 21 , wherein the aromatic-cationic peptide is administered intravenously, intradermally, intraperitoneally, subcutaneously, orally, transdermally, topically, intraocularly, iontophoretically, transmucosally, or by inhalation.
26 . The method of claim 21 , wherein the ischemia and/or reperfusion injury comprises vessel occlusion injury or cardiac ischemia-reperfusion injury.