METHODS AND COMPOSITIONS FOR TREATING MUSCLE DISEASE AND DISORDERS
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.