Compositions and methods for the modulation of JNK proteins
View Patent ↗The invention provides compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase 1 (JNK1 protein.
1. A method of reducing lipid levels in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of an antisense compound targeted to a JNK1 nucleic acid, thereby reducing lipid levels.
2. The method of claim 1 , wherein the administering further results in a reduction in glucose levels, body weight, adiposity, or an increase in metabolic rate or insulin sensitivity or any combination thereof.
3. The method of claim 1 , wherein the lipid levels are triglyceride or cholesterol or a combination thereof.
4. The method of claim 1 , wherein the subject has Type 2 diabetes.
5. The method of claim 2 , wherein the administering further results in reducing glucose levels or improving insulin sensitivity or both.
6. A method of treating obesity or metabolic syndrome in a subject comprising administering to said subject a lipid-lowering agent and a therapeutically effective amount of an antisense compound targeted to a JNK 1 nucleic acid, wherein said antisense compound targeted to said JNK 1 nucleic acid reduces lipid levels in said subject, thereby treating obesity or metabolic syndrome.
7. The method of claim 6 , wherein said lipid-lowering agent is a HMG-CoA reductase inhibitor or a cholesterol absorption inhibitor.
8. The method of claim 7 , wherein the HMG-CoA reductase inhibitor is a statin.
9. The method of claim 8 , wherein the statin is atorvastatin, simvastatin, pravastatin, fluvastatin or rosuvastatin.
10. The method of claim 7 , wherein the cholesterol absorption inhibitor is ezetimibe.
11. The method of claim 1 , wherein the administering comprises parenteral administration.
12. The method of claim 11 , wherein the parenteral administration comprises subcutaneous or intravenous administration.
13. The method of claim 1 , wherein the antisense compound is complementary to SEQ ID NO: 87, 89, 90 or 91.
14. The method of claim 1 , wherein the antisense compound is 12 to 30 nucleosides in length.
15. The method of claim 1 , wherein the antisense compound is an antisense oligonucleotide.
16. The method of claim 1 , wherein the antisense compound comprises at least one modified sugar moiety.
17. The method of claim 16 , wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
18. The method of claim 1 , wherein the antisense compound comprises at least one modified internucleoside linkage.
19. The method of claim 18 , wherein each internucleoside linkage of the antisense compound is a phosphorothioate internucleoside linkage.
20. The method of claim 1 , wherein the antisense compound comprises at least one modified nucleobase.
21. The method of claim 1 , wherein each cytosine of the antisense compound is a 5-methylcytosine.
22. The method of claim 1 , wherein the antisense compound is a gapmer antisense oligonucleotide.
23. The method of claim 22 , wherein the antisense compound is a gap-widened antisense oligonucleotide.
24. The method of claim 1 , wherein the antisense oligonucleotide comprises a gap segment of ten 2′-deoxynucleotides positioned between wing segments of five 2′-O-methoxyethyl modified nucleosides.
25. The method of claim 1 , wherein the subject has hyperlipidemia.
26. The method of claim 13 , wherein the antisense compound has 100% complementarity to SEQ ID NO: 87, 89, 90 or 91.
27. The method of claim 25 , wherein hyperlipidemia is hypercholesterolemia, hypertriglyceridemia or hyperfattyacidemia.
28. The method of claim 6 , wherein the administering further results in reducing glucose levels or improving insulin sensitivity or both.
29. The method of claim 1 , wherein the subject is obese.
30. The method of claim 1 , wherein the subject has metabolic syndrome.