Perhexiline for use in the treatment of hypertrophic cardiomyopathy (hcm)

Abstract

The invention relates to perhexiline, or a pharmaceutically acceptable salt or enantiomer thereof, for use in the treatment of hypertrophic cardiomyopathy, as well as to a method of treating HCM, which comprises administering to an animal in need thereof an effective amount of perhexiline, or a pharmaceutically acceptable salt or enantiomer thereof, to treat said HCM. The invention further relates to a treatment programme for treating HCM, which involves the co-use or co-administration of perhexiline with one or more other compounds that are advantageous in treating HCM or the symptoms thereof.

What is claimed is: 
     
         1 . A method for treating hypertrophic cardiomyopathy in a mammal in need thereof, comprising:
 diagnosing the mammal as having hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof; and   administering to said mammal a therapeutically-effective amount of (−)-perhexiline.   
     
     
         2 . The method of  claim 1 , wherein the therapeutically-effective amount of (−)-perhexiline is sufficient to reduce or ameliorate the hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof in the mammal. 
     
     
         3 . The method of  claim 1 , wherein the (−)-perhexiline is in the form of a pharmaceutically acceptable salt. 
     
     
         4 . The method of  claim 2 , wherein the (−)-perhexiline is in the form of a maleate salt. 
     
     
         5 . The method of  claim 1 , wherein the mammal is a human. 
     
     
         6 . The method of  claim 1 , further comprising co-administering to said mammal at least one therapeutic compound. 
     
     
         7 . The method of  claim 1 , further comprising co-administering to said mammal at least one therapeutic compound advantageous in treating hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof. 
     
     
         8 . The method of  claim 6 , wherein the therapeutic compound is selected from a member of the group consisting of Alpha Blockers, Beta Blockers, Calcium Channel Blockers, Diuretics, Ace (Angiotensin-Converting Enzyme) Inhibitors, Arb (Angiotensin II Receptor Blockers), Spironolactone, Nitrate, Warfarin, Verapamil, Insulin, Amiodarone, Lisinopril, Ramipril, Perindopril, Enalapril, Trandolapril, At2 Receptor Blockers, Losartan, Valsartan, Irbersartan, Carvedilol, Bisoprolol, Metoprolol, Atenolol, Aspirin, Clopidogrel, Oral Hypoglycaemics, Disopyramide, and Statins. 
     
     
         9 . A method for treating a mammal having at least one of a symptomatic component, feature or condition associated with hypertrophic cardiomyopathy, comprising:
 diagnosing the mammal as having at least one of a symptomatic component, feature or condition associated with hypertrophic cardiomyopathy; and   administering to said mammal a therapeutically-effective amount of (−)-perhexiline.   
     
     
         10 . The method of  claim 9 , wherein the symptomatic component, feature or condition is member of the group consisting of dyspnoea (shortness of breath), chest pain, fatigue, palpitation and syncope. 
     
     
         11 . The method of  claim 9 , wherein the mammal is further diagnosed as having a member of the group consisting of reduced left ventricular ejection fraction (LVEF), reduced E:EA ratio, abnormally rapid skeletal muscle phosphocreatine depletion with delayed recovery, reduced systolic velocity (PSV), diminished exercise capacity or tolerance, diminished peak oxygen consumption (VO 2 max) during exercise, diastolic dysfunction at rest and during exercise as measured by Time to Peak LV Filling (nTTPF), no significant LVOT obstruction at rest (gradient<30 mmHg), and impaired myocardial energetic state (PCr/γATP ratio). 
     
     
         12 . The method of  claim 9 , wherein the extent of hypertrophic cardiomyopathy in the mammal is diagnosed in accordance with a New York Heart Association (NYHA) classification. 
     
     
         13 . The method of  claim 9 , further comprising:
 determining a NYHA classification score (breathlessness) of the mammal before and after administration of perhexline, wherein a decreased NYHA score after administration of perhexline indicates a reduction in the extent of hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof in the mammal.   
     
     
         14 . The method of  claim 13 , wherein the NYHA classification score of the mammal after administration of (−)-perhexiline decreases from Class III to Class II. 
     
     
         15 . The method of  claim 9 , wherein the extent of hypertrophic cardiomyopathy in the mammal is diagnosed in accordance with a Minnesota Living with Heart Failure Questionnaire (MLHFQ) score. 
     
     
         16 . The method of  claim 15 , further comprising
 determining a MLHFQ (quality of life) score of the mammal before and after administration of (−)-perhexiline, wherein a decreased MLHFQ score after administration of (−)-perhexiline indicates a reduction in the extent of hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof in the mammal.   
     
     
         17 . The method of  claim 9 , further comprising determining peak oxygen consumption (VO 2 max) in the mammal during exercise wherein an increase in peak oxygen consumption (VO 2 max) in the mammal after administration of (−)-perhexiline indicates a reduction in the extent of hypertrophic cardiomyopathy or at least one of a symptomatic component, feature or condition thereof in the animal. 
     
     
         18 . The method of  claim 9 , wherein (−)-perhexiline is administered in an amount of 300 mg or less per day. 
     
     
         19 . The method of  claim 9 , wherein (−)-perhexiline is administered in an amount of 100 mg or less per day. 
     
     
         20 . The method of  claim 9 , wherein (−)-perhexiline is administered in an amount of 100 mg to 300 mg per day.