Compositions and methods to increase muscular strength
Provided herein are methods and compositions for increasing muscle strength, and for treating muscle wasting disorders, muscle degenerative disease, or exercise-induced weakness, and cancer.
1. A method for increasing muscle strength, comprising contacting a skeletal or smooth muscle of a subject in need thereof with a pharmacological agent comprising an F-actin disrupting agent at a dosage between about 0.01 to about 20 mg per kg of the subject applied for less than or equal to 5 hours to transiently depolymerize actin thereby reducing mechanical stiffness of a muscle tissue, wherein the F-actin disrupting agent comprises an actin nuclease inhibitor or tropomyosin inhibitor.
2. The method of claim 1 , wherein said actin nuclease inhibitor comprises SMIFH2 and wherein said tropomyosin inhibitor comprises ATM-3507.
3. The method of claim 1 , wherein said skeletal or smooth muscle is diseased or functionally compromised.
4. The method of claim 1 , wherein said subject comprises a muscle wasting disorder, a muscle degenerative disease, or exercise-induced muscle weakness.
5. The method of claim 1 , wherein said muscle strength is increased by at least 10% compared to the level of muscle strength prior to said contacting step.
6. The method of claim 1 , wherein an increase in muscle strength commences 0.1-5 hours post-administration.
7. The method of claim 1 , wherein the pharmacological agent comprises the F-actin disrupting agent at a dosage between about 0.3 to about 5 mg per kg of the subject.
8. The method of claim 1 , wherein the pharmacological agent comprising the F-actin disrupting agent is applied for about 2 hours.
9. A method for increasing muscle strength in a subject in need thereof, the method comprising:
contacting a skeletal muscle of the subject with an F-actin disrupting agent at a dosage between about 0.01 to about 20 mg per kg of the subject applied for less than or equal to 5 hours thereby transiently depolymerizing actin, wherein the F-actin disrupting agent comprises an actin nuclease inhibitor or tropomyosin inhibitor.
10. The method of claim 9 , wherein said skeletal muscle is diseased or functionally compromised, wherein said diseased or functionally compromised skeletal muscle is the result of a muscle wasting disorder, cancer, or exercise-induced muscle weakness.
11. The method of claim 10 , wherein the muscle wasting disorder comprises amyotrophic lateral sclerosis (ALS), Duchenne Muscular Dystrophy (DMD), cachexia, sarcopenia, human immunodeficiency syndrome (HIV), diabetes mellitus, or sepsis.
12. The method of claim 9 , wherein the skeletal muscle is healthy skeletal muscle.
13. The method of claim 9 , wherein said muscle strength is increased by at least 10% compared to the level of muscle strength prior to said contacting step.
14. The method of claim 9 , wherein an increase in muscle strength commences about 0.1-5 hours post-administration.
15. The method of claim 9 , wherein an increase in muscle strength commences about 24 hours post-administration.
16. The method of claim 9 , wherein the pharmacological agent comprises the F-actin disrupting agent at a dosage between about 0.3 to about 5 mg per kg of the subject.
17. The method of claim 9 , wherein the pharmacological agent comprising the F-actin disrupting agent is applied for about 2 hours.
18. A method of treating a subject who has a muscle wasting disorder, cancer, or exercise-induced muscle weakness, the method comprising:
administering a pharmaceutical composition comprising an F-actin disrupting agent at a dosage between about 0.01 to about 20 mg per kg of the subject applied for less than or equal to 5 hours to the subject thereby transiently depolymerizing actin, wherein the F-actin disrupting agent comprises an actin nuclease inhibitor or tropomyosin inhibitor.
19. The method of claim 18 , wherein the muscle wasting disorder comprises ALS, DMD, cachexia, sarcopenia, human immunodeficiency syndrome (HIV), diabetes mellitus, or sepsis.
20. The method of claim 18 , wherein the pharmacological agent comprises the F-actin disrupting agent at a dosage between about 0.3 to about 5 mg per kg of the subject.
21. The method of claim 18 , wherein the pharmacological agent comprising the F-actin disrupting agent is applied for about 2 hours.