US2018344797A1PendingUtilityA1

Methods for treatment of atherosclerosis

Assignee: STEALTH BIOTHERAPEUTICS CORPPriority: Aug 2, 2012Filed: Dec 20, 2017Published: Dec 6, 2018

Est. expiryAug 2, 2032(~6.1 yrs left)· nominal 20-yr term from priority

Inventors:D. Travis Wilson Mark Bamberger Brian Blakey

A61K 31/351A61K 31/366A61K 31/215A61K 31/22A61K 31/505A61K 31/40A61K 45/06A61K 38/07A61P 9/10A61K 31/404A61K 2300/00

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Claims

Abstract

Disclosed herein are methods and compositions for preventing or treating atherosclerosis in a mammalian subject. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide and, in some applications, a second active agent, to subjects in need thereof. The present technology relates to the treatment or prevention of atherosclerosis in mammals through the administration of a therapeutically effective amount of aromatic cationic peptides and, in some embodiments, a second active agent.

Claims

exact text as granted — not AI-modified

What is claimed is: 
     
         1 . A method for treating atherosclerosis in a mammalian subject in need thereof, the method comprising administering simultaneously, separately or sequentially an effective amount of (i) a peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof and (ii) an antihyperlipidemic drug. 
     
     
         2 . The method of  claim 1 , wherein the antihyperlipidemic drug is selected from the group consisting of: atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, clinofibrate, clofibrate, simfibrate, fenofibrate, bezafibrate, colestimide, colestyramine, ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         3 . The method of  claim 1 , wherein the antihyperlipidemic drug is a statin. 
     
     
         4 . The method of  claim 3 , wherein the statin is selected from the group consisting of: ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         5 . The method of  claim 1 , wherein the peptide and the antihyperlipidemic drug are administered simultaneously. 
     
     
         6 . The method of  claim 1 , wherein the peptide and the antihyperlipidemic drug are administered sequentially in either order. 
     
     
         7 . The method of  claim 1 , wherein treatment includes decreasing the size or number of atherosclerotic plaques in the subject, and/or decreasing the cholesterol content of an atherosclerotic plaque in the subject. 
     
     
         8 . A method for preventing atherosclerosis in a mammalian subject in need thereof, the method comprising administering simultaneously, separately or sequentially an effective amount of (i) a peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof and (ii) an antihyperlipidemic drug. 
     
     
         9 . The method of  claim 8 , wherein the antihyperlipidemic drug is selected from the group consisting of: atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, clinofibrate, clofibrate, simfibrate, fenofibrate, bezafibrate, colestimide, colestyramine, ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         10 . The method of  claim 8 , wherein the antihyperlipidemic drug is a statin. 
     
     
         11 . The method of  claim 10 , wherein the statin is selected from the group consisting of: ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         12 . The method of  claim 8 , wherein the peptide and the antihyperlipidemic drug are administered simultaneously. 
     
     
         13 . The method of  claim 8 , wherein the peptide and the antihyperlipidemic drug are administered sequentially in either order. 
     
     
         14 . The method of any one of  claims 8 - 13 , wherein the subject is predisposed to atherosclerosis. 
     
     
         15 . A method for ameliorating the signs, symptoms or complications of atherosclerosis, the method comprising administering simultaneously, separately or sequentially an effective amount of (i) a peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof and (ii) an antihyperlipidemic drug. 
     
     
         16 . The method of  claim 15 , wherein the signs, symptoms or complications of atherosclerosis include one or more selected from the group consisting of: elevated levels total cholesterol, VLDL cholesterol, LDL cholesterol, free cholesterol, cholesterol ester, phospholipids, triglycerides, and atherosclerotic lesions. 
     
     
         17 . The method of  claim 15 , wherein the antihyperlipidemic drug is selected from the group consisting of: atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, clinofibrate, clofibrate, simfibrate, fenofibrate, bezafibrate, colestimide, colestyramine, ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         18 . The method of  claim 15 , wherein the antihyperlipidemic drug is a statin. 
     
     
         19 . The method of  claim 18 , wherein the statin is selected from the group consisting of: ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         20 . The method of  claim 15 , wherein the peptide and the antihyperlipidemic drug are administered simultaneously. 
     
     
         21 . The method of  claim 15 , wherein the peptide and the antihyperlipidemic drug are administered sequentially in either order. 
     
     
         22 . The method of  claim 15 , wherein ameliorating the signs, symptoms or complications of atherosclerosis includes decreasing the size or number of atherosclerotic plaques in the subject, and/or decreasing the cholesterol content of an atherosclerotic plaque in the subject. 
     
     
         23 . A method for delaying onset, ameliorating or eliminating statin side effects in a subject in need thereof, the method comprising administering simultaneously, separately or sequentially with the statin, an effective amount of a peptide D-Arg-2′6′-Dmt-Lys-Phe-NH 2  or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The method of  claim 23 , wherein the statin side effect includes one or more of myopathy, rhabdomyolysis, kidney failure, diabetes, memory loss, decreased coenzyme Q10 levels and mitochondrial dysfunction. 
     
     
         25 . The method of  claim 23 , wherein the statin is selected from the group consisting of: atorvastatin, simvastatin, pravastatin, fluvastatin, lovastatin, pitavastatin, rosuvastatin, ADVICOR® (niacin extended-release/lovastatin), ALTOPREV® (lovastatin extended-release), CADUET® (amlodipine and atorvastatin), CRESTOR® (rosuvastatin), JUVISYNC® (sitagliptin/simvastatin), LESCOL® (fluvastatin), LESCOL XL (fluvastatin extended-release), LIPITOR® (atorvastatin), LIVALO® (pitavastatin), MEVACOR® (lovastatin), PRAVACHOL® (pravastatin), SIMCOR® (niacin extended-release/simvastatin), VYTORIN® (ezetimibe/simvastatin), and ZOCOR® (simvastatin). 
     
     
         26 . A method for increasing statin dosage in a subject in need thereof comprising: administering an effective amount of a statin at a first dosage level, and an aromatic-cationic peptide or a pharmaceutically acceptable salt thereof;
 evaluating the subject for side-effects characteristic of the statin, wherein the side-effects in the subject are reduced or absent as compared to a control subject administered the statin and not the aromatic cationic peptide;   administering a statin at a second dosage level, wherein the second dosage level is higher than the first statin dosage level.   
     
     
         27 . The method of  claim 26 , wherein the peptide is D-Arg-2′6′-Dmt-Lys-Phe-NH 2 . 
     
     
         28 . The method of  claim 26 , wherein the statin comprises LIPITOR® or CRESTOR®. 
     
     
         29 . The method of  claim 26 , wherein the side effect characteristic of the statin includes one or more of myopathy, rhabdomyolysis, kidney failure, diabetes, memory loss, decreased coenzyme Q10 levels and mitochondrial dysfunction. 
     
     
         30 . The method of any one of  claims 1 - 29 , wherein the pharmaceutically acceptable salt comprises acetate salt or trifluoroacetate salt.

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