Composition and method for treating or preventing skeletal muscle fibrosis

Abstract

A compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: wherein: R 1 is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2 is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3 is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and n is either 1 or 2; and pharmaceutically acceptable salts thereof; for use in treatment of or prevention of skeletal muscle fibrosis and/or for inducing skeletal muscle regeneration.

What is claimed is: 
     
         1 . A pharmaceutical composition for treating and/or preventing skeletal muscle fibrosis in a subject in need thereof, the composition comprising a pharmaceutically effective amount of a compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: 
       
         
           
           
               
               
           
         
       
       wherein: n is either 1 or 2
 R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2  is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and pharmaceutically acceptable salts thereof. 
 
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein said compound is halofuginone. 
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein said subject is suffering from a disorder which encompasses skeletal muscle tissue. 
     
     
         4 . A pharmaceutical composition according to  claim 3 , wherein said disorder is muscular dystrophy. 
     
     
         5 . A pharmaceutical composition according to  claim 4 , wherein said muscular dystrophy is selected from the group consisting of Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, and congenital muscular dystrophy. 
     
     
         6 . A pharmaceutical composition according to  claim 3 , wherein said disorder is denervation atrophy. 
     
     
         7 . A pharmaceutical composition according to  claim 3 , wherein said skeletal muscle tissue is diaphragm muscle. 
     
     
         8 . A pharmaceutical compositions for improving or inducing skeletal muscle regeneration in a subject in need thereof, the composition comprising a pharmaceutically effective amount of a compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: 
       
         
           
           
               
               
           
         
       
       wherein: n is either 1 or 2
 R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2  is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and pharmaceutically acceptable salts thereof. 
 
     
     
         9 . A pharmaceutical composition according to  claim 8 , wherein said compound is halofuginone. 
     
     
         10 . A pharmaceutical composition according to  claim 8 , wherein said subject is suffering from a disorder which targets skeletal muscle tissue. 
     
     
         11 . A pharmaceutical composition according to  claim 10 , wherein said disorder is muscular dystrophy. 
     
     
         12 . A pharmaceutical composition according to  claim 11 , wherein said muscular dystrophy is selected from the group consisting of Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, LimbGirdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, and congenital muscular dystrophy. 
     
     
         13 . A pharmaceutical composition according to  claim 10 , wherein said disorder is denervation atrophy. 
     
     
         14 . A pharmaceutical composition according to  claim 10 , wherein said skeletal muscle tissue is diaphragm muscle. 
     
     
         15 . A method for reducing the progression of skeletal muscle fibrosis in a subject in need thereof, the method comprising administering a pharmaceutically effective amount of a compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: 
       
         
           
           
               
               
           
         
       
       wherein: n is either 1 or 2
 R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2  is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and pharmaceutically acceptable salts thereof. 
 
     
     
         16 . A method according to  claim 15 , wherein said compound is halofuginone. 
     
     
         17 . A method according to  claim 15 , wherein said subject is suffering from a disorder which targets skeletal muscle tissue. 
     
     
         18 . A method according to  claim 17 , wherein said disorder is muscular dystrophy. 
     
     
         19 . A method according to  claim 18 , wherein said muscular dystrophy is selected from the group consisting of Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, and congenital muscular dystrophy. 
     
     
         20 . A method according to  claim 17 , wherein said disorder is denervation atrophy. 
     
     
         21 . A method according to  claim 17 , wherein said skeletal muscle tissue is diaphragm muscle. 
     
     
         22 . A method for improving or inducing skeletal muscle regeneration in a subject in need thereof, the method comprising administering a pharmaceutically effective amount of a compound in combination with a pharmaceutically acceptable carrier, the compound having a formula: 
       
         
           
           
               
               
           
         
       
       wherein: n is either 1 or 2
 R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2  is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and pharmaceutically acceptable salts thereof. 
 
     
     
         23 . A method according to  claim 22 , wherein said compound is halofuginone. 
     
     
         24 . A method according to  claim 22 , wherein said subject is suffering from a disorder which targets skeletal muscle tissue. 
     
     
         25 . A method according to  claim 24 , wherein said disorder is muscular dystrophy. 
     
     
         26 . A method according to  claim 25 , wherein said muscular dystrophy is selected from the group consisting of Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, and congenital muscular dystrophy. 
     
     
         27 . A pharmaceutical composition according to  claim 24 , wherein said disorder is denervation atrophy. 
     
     
         28 . A pharmaceutical composition according to  claim 24 , wherein said skeletal muscle tissue is diaphragm muscle. 
     
     
         29 . A method according to  claim 22 , wherein the improving of skeletal muscle regeneration occurs through inhibiting the TGFβ pathway and/or by inhibiting the Myostatin Smad3-dependent pathway. 
     
     
         30 . Use of a compound having a formula: 
       
         
           
           
               
               
           
         
       
       wherein: n is either 1 or 2
 R 1  is a member of the group consisting of hydrogen, halogen, nitro, benzo, lower alkyl, phenyl, and lower alkoxy; R 2  is a member of the group consisting of hydroxy, acetoxy, and lower alkoxy; and R 3  is a member of the group consisting of hydrogen and lower alkenoxy-carbonyl; and pharmaceutically acceptable salts thereof; 
 in the manufacture of a medicament for reducing the progression of skeletal muscle fibrosis in a subject in need thereof. 
 
     
     
         31 . The use according to  claim 30 , wherein said compound is halofuginone. 
     
     
         32 . The use according to  claim 30 , wherein said subject is suffering from a disorder which targets skeletal muscle tissue. 
     
     
         33 . The use according to  claim 32 , wherein said disorder is muscular dystrophy. 
     
     
         34 . The use according to  claim 33 , wherein said muscular dystrophy is selected from the group consisting of Duchenne muscular dystrophy, Becker muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Limb-Girdle Muscular Dystrophy, Facioscapulohumeral Muscular Dystrophy, Myotonic Dystrophy, Oculopharyngeal Muscular Dystrophy, Distal Muscular Dystrophy, and congenital muscular dystrophy. 
     
     
         35 . The use according to  claim 32 , wherein said disorder is denervation atrophy. 
     
     
         36 . The use according to  claim 32 , wherein said skeletal muscle tissue is diaphragm muscle.