Targeting microRNAs for metabolic disorders
Described herein are compounds comprising modified oligonucleotides that are complementary to miR-103 and/or miR-107 and methods of treating diseases and disorders using the compounds.
1. A method of treating at least one metabolic disorder in a subject or preventing or delaying the onset of at least one metabolic disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound comprising the structure:
wherein X is a phosphodiester linkage; each N of N m is a deoxyadenosine (A); m is 2; Y is a phosphodiester linkage; and MO is 5′-C S A S A S U S G S C S U S G S C S A S AAC S A S A S U S G S C S U S G S C S A S -3′ (SEQ ID NO: 7), wherein each nucleoside followed by a subscript “S” is a S-cEt nucleoside, each nucleoside not followed by a subscript is a deoxynucleoside, and each internucleoside linkage between two S-cEt nucleosides is a phosphorothioate linkage, and the remaining internucleoside linkages are phosphodiester linkages; and wherein Y is linked to the 3′ terminus of MO.
2. The method of claim 1 , wherein at least one metabolic disorder is selected from pre-diabetes, diabetes, metabolic syndrome, obesity, diabetic dyslipidemia, hyperlipdemia, hypertension, hypertriglyceridemia, hyperfattyacidemia, hypercholesterolemia, and hyperinsulinemia.
3. The method of claim 2 , wherein the diabetes is type 2 diabetes.
4. The method of claim 1 , wherein the subject has fatty liver disease.
5. The method of claim 4 , wherein the fatty liver disease is selected from non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, alcoholic steatohepatitis, and non-alcoholic steatohepatitis (NASH).
6. The method of claim 4 , wherein the subject has non-alcoholic steatohepatitis (NASH).
7. The method of claim 6 , wherein the subject has type 2 diabetes.
8. The method of claim 1 , wherein the compound is comprised in a pharmaceutical composition.
9. The method of claim 8 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
10. The method of claim 9 , wherein the pharmaceutical composition is an aqueous composition.
11. The method of claim 7 , wherein the compound is comprised in a pharmaceutical composition.
12. The method of claim 11 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
13. The method of claim 12 , wherein the pharmaceutical composition is an aqueous composition.
14. A method of treating at least one metabolic disorder in a subject or preventing or delaying the onset of at least one metabolic disorder in a subject, comprising administering to the subject a therapeutically effective amount of a compound having the structure:
15. The method of claim 14 , wherein at least one metabolic disorder is selected from pre-diabetes, diabetes, metabolic syndrome, obesity, diabetic dyslipidemia, hyperlipdemia, hypertension, hypertriglyceridemia, hyperfattyacidemia, hypercholesterolemia, and hyperinsulinemia.
16. The method of claim 15 , wherein the diabetes is type 2 diabetes.
17. The method of claim 14 , wherein the subject has fatty liver disease.
18. The method of claim 17 , wherein the fatty liver disease is selected from non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, alcoholic steatohepatitis, and non-alcoholic steatohepatitis (NASH).
19. The method of claim 17 , wherein the subject has non-alcoholic steatohepatitis (NASH).
20. The method of claim 19 , wherein the subject has type 2 diabetes.
21. The method of claim 16 , wherein the compound is comprised in a pharmaceutical composition.
22. The method of claim 21 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
23. The method of claim 22 , wherein the pharmaceutical composition is an aqueous composition.
24. The method of claim 20 , wherein the compound is comprised in a pharmaceutical composition.
25. The method of claim 24 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.
26. The method of claim 25 , wherein the pharmaceutical composition is an aqueous composition.