Compositions and methods for treating and preventing skeletal muscle deficiencies
The present invention relates to compositions and methods for treating and preventing skeletal muscle deficiencies. In particular, the present invention provides compositions comprising poloxamers (e.g., poloxamer 188-P188) and methods of using the same for treating and preventing skeletal muscle deficiencies and injuries (e.g., dystrophin-deficient skeletal muscle; skeletal muscle having a contraction force deficit; skeletal muscle having a Ca 2+ imbalance; skeletal muscle having microtears).
1. A method of treating a subject to prevent or reduce an exercise induced skeletal muscle injury or prevent or reduce a skeletal muscle deficiency, comprising administering to said subject a composition comprising a poloxamer under conditions such that said skeletal muscle injury or deficiency is reduced or prevented, wherein said skeletal muscle deficiency is selected from one or more of the following: a dystrophin-deficient skeletal muscle or a skeletal muscle having a contraction force deficit.
2. The method of claim 1 , wherein said skeletal muscle deficiency is a skeletal muscle contraction force deficit.
3. The method of claim 1 , wherein said poloxamer is a purified or fractionated poloxamer.
4. The method of claim 1 , wherein said subject is a human subject.
5. The method of claim 1 , wherein said composition is administered via intravenous administration.
6. The method of claim 1 , wherein said subject is a dystrophin deficient subject.
7. The method of claim 6 , wherein said subject has Duchene's muscular dystrophy.
8. The method of claim 1 , wherein said poloxamer is P188.
9. The method of claim 1 , wherein said poloxamer is administered at a dosage level of approximately between 420-500 mg per kg weight of said subject.
10. The method of claim 9 , wherein said dosage level is 460 mg per kg weight of said subject.
11. The method of claim 1 , wherein said composition comprising a poloxamer is co-administered with one or more agents selected from the group consisting of streptomyocin, prednisone, deflazacort, azathioprine, cyclosporine, valproic acid, phenylbutyrate, sodium butyrate, M344, suberoylanilide hydroxamic acid, and PCT124.
12. The method of claim 1 , wherein said skeletal muscle comprises at least one skeletal muscle selected from the group consisting of gastrocnemius, tibialis posterior, soleus, longus, brevis, gluteus maximus muscle, biceps femoris, semitendinosus, semimembranosus, iliopsoas, quadriceps femoris, adductor muscles of the hip, levator scapulae, trapezius, rectus abdominis, transversus abdominis, abdominal external oblique muscle, abdominal internal oblique muscle, erector spinae, pectoralis major, biceps brachii, triceps brachii, brachialis, pronator teres, brachioradialis, rhomboids, deltoid, latissimus dorsi, rotator cuff, and lumbrical muscle.
13. A composition comprising a poloxamer and a second agent useful for the treatment of a skeletal muscle contraction force deficit.
14. The composition of claim 13 , wherein said agent useful for the treatment of a skeletal muscle contraction force deficit is selected from the group consisting of streptomycin, prednisone, deflazacort, azathioprine, cyclosporine, valproic acid, phenylbutyrate, sodium butyrate, M344, suberoylanilide hydroxamic acid, and PCT124, or a combination of these agents.
15. The composition of claim 13 , wherein said poloxamer is P188.
16. The composition of claim 13 , wherein said poloxamer is selected from the group consisting of P138, P237, P288, P124, P338, and P407.
17. The composition of claim 13 , wherein said skeletal muscle comprises the lumbrical muscle.
18. The composition of claim 14 , wherein said skeletal muscle comprises at least one skeletal muscle selected from the group consisting of gastrocnemius, tibialis posterior, soleus, longus, brevis, gluteus maximus muscle, biceps femoris, semitendinosus, semimembranosus, iliopsoas, quadriceps femoris, adductor muscles of the hip, levator scapulae, trapezius, rectus abdominis, transversus abdominis, abdominal external oblique muscle, abdominal internal oblique muscle, erector spinae, pectoralis major, biceps brachii, triceps brachii, brachialis, pronator teres, brachioradialis, rhomboids, deltoid, latissimus dorsi, and rotator cuff.
19. The method of claim 1 , wherein a poloxamine and/or a polyglycidol is used instead of, or with, said poloxamer.
20. The composition of claim 13 , wherein a poloxamine and/or a polyglycidol is used instead of, or with, said poloxamer.