Inhibitors of Phosphodiesterase Type 5A for Treating or Preventing Muscle Disease or the Symptoms Thereof in a Patient

Abstract

Disclosed are pharmaceutical compositions and methods for treating or preventing muscle diseases or the symptoms thereof. The compositions typically include and the methods typically utilize phosphodiesterase type 5A inhibitors.

1 . A method for treating muscular dystrophy in a patient, the method comprising administering to the patient an effective amount of sildenafil, a sildenafil analog, a sildenafil derivative, or a pharmaceutical salt thereof having phosphodiesterase type 5A inhibitory activity. 
     
     
         2 . The method of  claim 1 , comprising administering sildenafil citrate to the patient. 
     
     
         3 . The method of  claim 1  for treating DMD, BMD, CMD/LGMD, LGMD-2A, LGMD-2B, LGMD-2D, LGMD-2E, LGMD-2I, muscle diseases associated with mutations in the δ-sarcoglycan gene, Ullrich congential muscular dystrophy (UCMD), congenital merosin-deficient 1A (MDC1A) muscular dystrophy, myositis, autophagic vacuolar myopathy, myopathies not associated with a specific protein deficiency, myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA), critical care myopathy cases, Pompe disease, or sarcoidosis. 
     
     
         4 . The method of  claim 1  for treating DMD. 
     
     
         5 . The method of  claim 1  for treating BMD. 
     
     
         6 . The method of  claim 1 , wherein the effective amount is effective for reducing fatigue in the patient. 
     
     
         7 . The method of  claim 1 , wherein the effective amount is effective for reducing activity-induced fatigue in the patient. 
     
     
         8 . The method of  claim 1 , wherein the effective amount is effective for reducing fatigue in the patient after exercise and the effective amount is administered to the patient prior to exercise. 
     
     
         9 . The method of  claim 8 , wherein the exercise is mild exercise. 
     
     
         10 . The method of  claim 1  for reducing muscle fatigue. 
     
     
         11 . The method of  claim 1 , wherein the effective amount is effective for reducing muscle damage in the patient. 
     
     
         12 . The method of  claim 1 , wherein the sildenafil, the sildenafil analog, the sildenafil derivative, or the pharmaceutical salt thereof is administered daily at a dose of about 10-30 mg/kg body mass. 
     
     
         13 . A method for reducing fatigue in a patient having a muscle disease, the method comprising administering an effective amount of a phosphodiesterase type 5A inhibitor or a pharmaceutical salt thereof to the patient. 
     
     
         14 . The method of  claim 13  for reducing activity-induced fatigue in the patient. 
     
     
         15 . The method of  claim 13  for reducing fatigue in the patient after exercise, wherein the phosphodiesterase type 5A inhibitor or the pharmaceutical salt thereof is administered to the patient prior to exercise. 
     
     
         16 . The method of  claim 15 , wherein the exercise is mild exercise. 
     
     
         17 . The method of  claim 13  for reducing muscle fatigue. 
     
     
         18 . The method of  claim 13 , wherein the patient has or is at risk for acquiring DMD, BMD, CMD/LGMD, LGMD-2A, LGMD-2B, LGMD-2D, LGMD-2E, LGMD-2I, muscle diseases associated with mutations in the δ-sarcoglycan gene, Ullrich congential muscular dystrophy (UCMD), congenital merosin-deficient 1A (MDC1A) muscular dystrophy, myositis, autophagic vacuolar myopathy, myopathies not associated with a specific protein deficiency, myotonic dystrophy type 1(DM1), spinal muscular atrophy (SMA), critical care myopathy cases, Pompe disease, or sarcoidosis. 
     
     
         19 . The method of  claim 13 , wherein the muscle disease is muscular dystrophy. 
     
     
         20 . The method of  claim 19 , wherein the patient has Duchenne muscular dystrophy. 
     
     
         21 . The method of  claim 19 , wherein the patient has Becker muscular dystrophy. 
     
     
         22 . The method of  claim 13 , wherein the phosphodiesterase type 5A inhibitor is sildenafil, a sildenafil analog, a sildenafil derivative, or a pharmaceutical salt thereof. 
     
     
         23 . The method of  claim 13 , wherein the phosphodiesterase type 5A inhibitor is sildenafil citrate. 
     
     
         24 . The method of  claim 13 , wherein the phosphodiesterase type 5A inhibitor is tadalafil, a tadalafil analog, a tadalafil derivative, a tadalafil isomer, or a pharmaceutical salt thereof. 
     
     
         25 . The method of  claim 13 , wherein the phosphodiesterase type 5A inhibitor is administered at a dosage of about 10-30 mg/kg body mass. 
     
     
         26 . The method of  claim 15 , wherein the phosphodiesterase type 5A inhibitor is administered no later than about 24 hours before exercise. 
     
     
         27 . The method of  claim 15 , wherein the phosphodiesterase type 5A inhibitor is administered no later than about 6 hours before exercise. 
     
     
         28 . A method for reducing the likelihood of edema occurring after exercise in a patient having a muscle disease, the method comprising administering to the patient an effective amount of sildenafil, a sildenafil analog, a sildenafil derivative, or a pharmaceutical salt thereof having phosphodiesterase type 5A inhibitory activity prior to exercise. 
     
     
         29 . The method of  claim 28 , wherein the exercise is mild exercise. 
     
     
         30 . The method of  claim 28 , wherein the patient has a muscle disease selected from a group consisting of DMD, BMD, CMD/LGMD, LGMD-2A, LGMD-2B, LGMD-2D, LGMD-2E, LGMD-2I, muscle diseases associated with mutations in the δ-sarcoglycan gene, Ullrich congential muscular dystrophy (UCMD), congenital merosin-deficient 1A (MDC1A) muscular dystrophy, myositis, autophagic vacuolar myopathy, myopathies not associated with a specific protein deficiency, myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA), critical care myopathy cases, Pompe disease, or sarcoidosis. 
     
     
         31 . The method of  claim 28 , wherein the patient has muscular dystrophy. 
     
     
         32 . The method of  claim 31 , wherein the patient has Duchenne muscular dystrophy. 
     
     
         33 . The method of  claim 31 , wherein the patient has Becker muscular dystrophy. 
     
     
         34 . The method of  claim 28  comprising administering an effective amount of sildenafil citrate.