Aromatic-cationic peptides and uses of same

Abstract

The present disclosure provides aromatic-cationic peptide compositions and methods of using the same. The methods comprise use of the peptides in electron transport, inhibition of cardiolipin peroxidation, and inhibition of apoptosis and necrosis to treat, prevent or ameliorate the symptoms of autoimmune diseases or condition.

1 . A method for treating a subject suffering from an autoimmune disease characterized by an increased level of cardiolipin antibody, comprising: administering a therapeutically effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof to the subject. 
     
     
         2 . The method of  claim 1 , wherein the aromatic cationic peptide comprises one or more peptides selected from the group consisting of 2′,6′-Dmt-D-Arg-Phe-Lys-NH2, Phe-D-Arg-Phe-Lys-NH 2 , D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 , 2′,6′ Dmt-D Arg-Phe-(atn)Dap-NH 2 , where (atn)Dap is β-anthraniloyl-L-α,β-diaminopropionic acid, and 2′,6′-Dmt-D-Arg-Ald-Lys-NH 2 , where Ald is β-(6′-dimethylamino-2′-naphthoyl)alanine. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1  wherein the peptide comprises D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 . 
     
     
         5 . The method of  claim 1 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus and antiphospholipid syndrome. 
     
     
         6 . The method of  claim 5 , wherein treatment comprises reducing or ameliorating one or more symptoms of systemic lupus erythematosus, wherein the symptoms of systemic lupus erythematosus are one or more selected from the group consisting of: increased cardiolipin antibody levels, fever, vascular thrombosis, thrombocytopenia, heart valve disease, livedo reticularis, pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, shrinking lung syndrome, pericarditis, myocarditis, endocarditis, anemia, low platelet and white cell count, prolonged partial thromboplastin time, osteoarticular tuberculosis, myalgia, malar rash, discoid lupus, allopecia, mouth, nasal, urinary tract and vaginal ulcers, polyneuropathy, and intracranial hypertension syndrome. 
     
     
         7 . The method of  claim 1 , wherein the aromatic-cationic peptide is administered orally, parenterally, intravenously, subcutaneously, transdermally or by inhalation. 
     
     
         8 . A method for reducing cardiolipin oxidation in a subject suffering from an autoimmune disease comprising: administering an effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof to the subject. 
     
     
         9 . The method of  claim 8 , wherein the aromatic cationic peptide is one or more selected from of 2′6′-Dmt-D-Arg-Phe-Lys-NH 2 , Phe-D-Arg-Phe-Lys-NH 2 , D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 , Dmt-D-Arg-Phe-(atn)Dap-NH 2 , where (atn)Dap is β-anthraniloyl-L-α,β-diaminopropionic acid, and 2′,6′-Dmt-D-Arg-Ald-Lys-NH 2 , where Ald is β-(6′-dimethylamino-2′-naphthoyl)alanine. 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 8 , wherein the autoimmune disease is characterized by an increased level of antibodies against cardiolipin. 
     
     
         12 . The method of  claim 8 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus and antiphospholipid syndrome. 
     
     
         13 . The method of  claim 12 , wherein the method comprises reducing or ameliorating one or more symptoms of systemic lupus erythematosus, wherein the symptoms of systemic lupus erythematosus are one or more selected from the group consisting of: increased cardiolipin antibody levels, fever, vascular thrombosis, thrombocytopenia, heart valve disease, livedo reticularis, pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, shrinking lung syndrome, pericarditis, myocarditis, endocarditis, anemia, low platelet and white cell count, prolonged partial thromboplastin time, osteoarticular tuberculosis, myalgia, malar rash, discoid lupus, allopecia, mouth, nasal, urinary tract and vaginal ulcers, polyneuropathy, and intracranial hypertension syndrome. 
     
     
         14 . The method of  claim 8 , wherein the aromatic-cationic peptide is administered orally, parenterally, intravenously, subcutaneously, transdermally or by inhalation. 
     
     
         15 . A method for reducing inflammation in subject suffering from an autoimmune disease comprising: administering an effective amount of an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof to a subject that has an autoimmune disease. 
     
     
         16 . The method of  claim 15 , wherein the aromatic cationic peptide is one or more selected from the group consisting of 2′,6′-Dmt-D-Arg-Phe-Lys-NH 2 , Phe-D-Arg-Phe-Lys-NH 2 , D-Arg-2′,6′-Dmt-Lys-Phe-NH 2 , 2′,6′-Dmt-D-Arg-Phe-(atn)Dap-NH 2 , where (atn)Dap is β-anthraniloyl-L-α,β-diaminopropionic acid, and 2′,6′-Dmt-D-Arg-Ald-Lys-NH 2 , where Ald is β-(6′-dimethylamino-2′-naphthoyl)alanine. 
     
     
         17 . (canceled) 
     
     
         18 . The method of  claim 15 , wherein the autoimmune disease produces antibodies against cardiolipin. 
     
     
         19 . The method of  claim 15 , wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus and antiphospholipid syndrome. 
     
     
         20 . The method of  claim 19 , wherein the method comprises reducing or ameliorating one or more symptoms of systemic lupus erythematosus, wherein the symptoms of systemic lupus erythematosus are one or more selected from the group consisting of: increased cardiolipin antibody levels, fever, vascular thrombosis, thrombocytopenia, heart valve disease, livedo reticularis, pleuritis, pleural effusion, lupus pneumonitis, chronic diffuse interstitial lung disease, pulmonary hypertension, pulmonary emboli, pulmonary hemorrhage, shrinking lung syndrome, pericarditis, myocarditis, endocarditis, anemia, low platelet and white cell count, prolonged partial thromboplastin time, osteoarticular tuberculosis, myalgia, malar rash, discoid lupus, allopecia, mouth, nasal, urinary tract and vaginal ulcers, polyneuropathy, and intracranial hypertension syndrome. 
     
     
         21 . The method of  claim 15 , wherein the aromatic-cationic peptide is administered orally, parenterally, intravenously, subcutaneously, transdermally or by inhalation. 
     
     
         22 . (canceled) 
     
     
         23 . The method of  claim 1 , wherein the peptide comprises 2′,6′-Dmt-D-Arg-Phe-(atn)Dap-NH 2 , where (atn)Dap is β-anthraniloyl-L-α,β-diaminopropionic acid. 
     
     
         24 . The method of  claim 1 , wherein the peptide comprises 2′,6′-Dmt-D-Arg-Ald-Lys-NH 2 , where Ald is β-(6′-dimethylamino-2′-naphthoyl)alanine.