Methods for use in modulating miR-122A
Methods are provided for the treatment of cardiovascular or metabolic diseases characterized by elevated serum total cholesterol, elevated serum LDL-cholesterol, or elevated serum triglycerides, through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Further provided are methods for reducing hepatic steatosis or liver tissue triglyceride accumulation through the administration of an oligomeric compound which modulates the levels or activity of miR-122a. Such methods employ oligomeric compounds which hybridize with or sterically interfere with nucleic acid molecules comprising or encoding miR-122a. Such oligomeric compounds may include one or more modifications thereon, which may improve the activity, stability, or nuclease resistance of the oligomeric compound. These modified oligomeric compounds are used as single compounds or in compositions, including pharmaceutical compositions, to modulate or mimic the targeted nucleic acid comprising or encoding miR-122a.
1. A method of treating non-alcoholic fatty liver disease in a human comprising administering to a human with non-alcoholic fatty liver disease a therapeutically effective amount of an antisense compound having at least 90% nucleobase sequence complementarity to miR-122a (SEQ ID NO: 3).
2. The method of claim 1 wherein the non-alcoholic fatty liver disease is hepatic steatosis.
3. The method of claim 1 , wherein the antisense compound is fully complementary to miR-122a (SEQ ID NO: 3).
4. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide.
5. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide 15 to 30 linked nucleosides in length.
6. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide 17 to 25 linked nucleosides in length.
7. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide 19 to 23 nucleosides in length.
8. The method of claim 1 , wherein the antisense compound comprises at least one modified sugar moiety.
9. The method of claim 8 , wherein the modified sugar moiety is a 2′-O-methoxyethyl nucleoside.
10. The method of claim 8 , wherein the modified sugar moiety is a bicyclic sugar moiety.
11. The method of claim 1 , wherein the antisense compound comprises a plurality of modified sugar moieties.
12. The method of claim 11 , wherein the antisense compound comprises a plurality of 2′-O-methoxyethyl sugar moieties and a plurality of bicyclic sugar moieties.
13. The method of claim 1 , wherein the antisense compound comprises at least one phosphorothioate internucleoside linkage.
14. The method of claim 1 , wherein the antisense compound comprises at least one 5-methyl cytosine.
15. The method of claim 1 , wherein the method comprises selecting a human having non-alcoholic fatty liver disease.
16. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide linked to a conjugate group.
17. The method of claim 16 , wherein the conjugate group comprises a carbohydrate.
18. The method of claim 1 wherein the non-alcoholic fatty liver disease is non-alcoholic steatohepatitis.