Methods and compositions for treating muscle disease and disorders

Abstract

The present disclosure provides a method of treating muscle myopathy, including muscle dystrophies and cardiomyopathies, by administering stable, long-lasting vasoactive intestinal peptide therapeutic agents. These agents include one or more elastin-like peptides and can be administered at a low-dose.

1 - 59 . (canceled) 
     
     
         60 . A method for treating muscle myopathy in a patient in need thereof comprising administering to said patient a pharmaceutical composition comprising a VPAC2-selective Vasoactive Intestinal Peptide (VIP) and an elastin-like peptide comprising at least 90 repeating units of VPGXG (SEQ ID NO: 3), where X is independently selected from Val, Ala, and Gly at a ratio of about 5:3:2. 
     
     
         61 . The method of  claim 60 , wherein administration of the pharmaceutical composition reduces muscle fibrosis, preserves muscle contractility, or preserves muscle strength in the patient. 
     
     
         62 . The method of  claim 60 , wherein administration of the pharmaceutical composition protects against muscle contraction-induced injury in the patient. 
     
     
         63 . The method of  claim 60 , wherein the muscle myopathy is cardiomyopathy or skeletal muscle myopathy. 
     
     
         64 . The method of  claim 60 , wherein the pharmaceutical composition is formulated for subcutaneous, intramuscular, or intravenous administration. 
     
     
         65 . The method of  claim 60 , wherein the pharmaceutical composition is administered at a low dose. 
     
     
         66 . The method of claim  1 , wherein the pharmaceutical composition is administered at a dose between 1 mg/kg per day and 10 mg/kg per day. 
     
     
         67 . The method of  claim 60 , wherein the pharmaceutical composition is administered daily, from one to three times weekly, weekly, or from one to two times a month. 
     
     
         68 . The method of  claim 60 , wherein administration of the pharmaceutical formulation preserves:
 a) myocyte shortening compared to that of an untreated myocyte;   b) myocyte contractility compared to that of an untreated myocyte;   c) myocyte re-lengthening velocity compared to that of an untreated myocyte; or   d) myocyte relaxation compared to that of an untreated myocyte.   
     
     
         69 . The method of  claim 68 , wherein the myocyte is a cardiomyocyte. 
     
     
         70 . The method of  claim 68 , wherein the myocyte is a skeletal muscle myocyte. 
     
     
         71 . The method of  claim 60 , wherein the patient has muscular dystrophy, cardiomyopathy, or an inflammatory myopathy. 
     
     
         72 . The method of  claim 71 , wherein the muscular dystrophy is selected from the group consisting of Myotonic muscular dystrophy, Duchenne muscular dystrophy, Becker muscular dystrophy, Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, Congenital muscular dystrophy, Oculopharyngeal muscular dystrophy, Distal muscular dystrophy, and Emery-Dreifuss muscular dystrophy. 
     
     
         73 . The method of  claim 71 , wherein the inflammatory myopathy is selected from the group consisting of polymyositis, dermatomyositis, and inclusion body myositis. 
     
     
         74 . The method of  claim 71 , wherein the cardiomyopathy results from a muscular dystrophy. 
     
     
         75 . The method of  claim 74 , wherein the muscular dystrophy is Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, or X-linked dilated cardiomyopathy. 
     
     
         76 . The method of  claim 60 , wherein the pharmaceutical composition comprises SEQ ID NO: 15. 
     
     
         77 . The method of  claim 60 , wherein administration of the pharmaceutical composition:
 a) increases the ventricular filling velocity compared to an untreated myopathic patient;   b) elevates the maximal rate of pressure rise compared to an untreated myopathic patient;   c) increases the Tau constant of relaxation compared to an untreated myopathic patient;   d) decreases the collagen content in a muscle compared to an untreated myopathic patient; or   e) decreases immune cell count in muscle compared to an untreated myopathic patient.   
     
     
         78 . The method of claim  1 , wherein the immune cells is a macrophage.