Compositions comprising MG29 nucleic acids, polypeptides, and associated methods of use
View Patent ↗Disclosed herein are compositions and methods for treatment of muscle dysfunction (including sarcopenia) and other diseases involving skeletal muscle, including age-related muscle dysfunction. In addition, the invention relates to therapeutic compositions comprising nucleotides and/or polypeptides of the invention in combination with a pharmaceutically acceptable carrier, wherein the composition facilitates the treatment of skeletal muscle disorder, including those related to thr normal aging process. Moreover, the invention relates to the treatment and/or prevention of pathological conditions associated with altered intracellular Ca2+ regulation and disrupted membrane structure that occurs when the expression levels of MG29 are reduced.
1. A method of modulating muscle contractile function comprising administering to a subject in need thereof a composition comprising a pharmaceutically acceptable carrier and an effective amount of an agent that modulates mitsugumin29 (MG29) in a muscle cell, wherein the agent is at least one of (i) a nucleic acid that encodes an MG29 polypeptide, or (ii) a nucleic acid that hybridizes specifically to an MG29 mRNA transcript, and wherein the agent is effective in modulating MG29, and thereby, modulates muscle contractile function.
2. The method of claim 1 , wherein the effective amount is from 0.1 mg/kg and 1000 mg/kg body weight/day.
3. The method of claim 1 , wherein the composition further includes a nucleic acid that inhibits the expression or activity of an MG29 mRNA binding protein.
4. The method of claim 3 , wherein the MG29 mRNA binding protein interacts with either the 5′ or the 3′ UTR of the MG29 mRNA transcript.
5. The method of claim 1 , wherein the MG29 polypeptide is selected from the group consisting of SEQ ID NOs.: 1-20, or a bioactive portion thereof.
6. The method of claim 1 , wherein the nucleic acid encoding an MG29 polypeptide demonstrates at least 85% sequence identity to a nucleic acid selected from the group consisting of SEQ ID NOs.: 21-26.
7. The method of claim 1 , wherein the nucleic acid of (ii) is an inhibitory RNA or an antisense RNA.
8. The method of claim 7 , wherein the inhibitory RNA is a small inhibitory RNA or a microRNA.
9. A method of treating sarcopenia comprising identifying an individual in need thereof, and administering to an individual a composition comprising a pharmaceutically acceptable carrier and an effective amount of an agent that modulates mitsugumin29 (MG29), in a muscle cell, wherein the agent is at least one of (i) a nucleic acid that encodes an MG29 polypeptide, or (ii) a nucleic acid that hybridizes specifically to an MG29 mRNA transcript, and wherein the agent is effective in modulating MG29, and thereby, treats sarcopenia.
10. The method of claim 9 , wherein the composition is administered systemically.
11. The method of claim 9 , wherein the agent (i) comprises a nucleic acid encoding an MG29 polypeptide as set forth in SEQ ID NOs.: 1-8, or 26.
12. The method of claim 11 , wherein the nucleic acid encodes an MG29 polypeptide as set forth in SEQ ID NO:3.
13. The method of claim 9 , wherein the composition further includes a nucleic acid that inhibits the expression or activity of an MG29 mRNA binding protein.
14. The method of claim 13 , wherein the inhibitory nucleic acid comprises RNA.
15. The method of claim 14 , wherein the inhibitory RNA is at least one of an antisense RNA, an interfering RNA or combination of both.
16. The method of claim 15 , wherein the interfering RNA is at least one of an siRNA, an miRNA or combination thereof.