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 clastin-like peptides and can be administered at a low-dose.
1. A method for slowing skeletal muscle deterioration in a patient having muscular dystrophy comprising administering to a patient in need thereof 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.
2. The method of claim 1 , wherein administration of the pharmaceutical composition reduces muscle fibrosis, preserves muscle contractility, or preserves muscle strength in the patient.
3. The method of claim 1 , wherein administration of the pharmaceutical composition protects against muscle contraction-induced injury in the patient.
4. The method of claim 1 , wherein the muscle myopathy is skeletal muscle myopathy.
5. The method of claim 1 , wherein the pharmaceutical composition is formulated for subcutaneous, intramuscular, or intravenous administration.
6. The method of claim 1 , wherein the pharmaceutical composition is administered at a low dose.
7. 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.
8. The method of claim 1 , wherein the pharmaceutical composition is administered daily, from one to three times weekly, weekly, or from one to two times a month.
9. The method of claim 1 , 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.
10. The method of claim 9 , wherein the myocyte is a skeletal muscle myocyte.
11. The method of claim 1 , wherein the skeletal 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.
12. The method of claim 11 , wherein the muscular dystrophy is Duchenne Muscular Dystrophy or Becker Muscular Dystrophy.
13. The method of claim 1 , wherein the pharmaceutical composition comprises SEQ ID NO: 15.
14. The method of claim 1 , wherein administration of the pharmaceutical composition:
a) decreases the collagen content in a muscle compared to an untreated myopathic patient; or
b) decreases immune cell count in muscle compared to an untreated myopathic patient.
15. The method of claim 14 , wherein the immune cells is a macrophage.