Downregulating mir-132 for the treatment of lipid related disorders

Abstract

A method of treating a lipid-related disorder in a subject in need thereof is disclosed. The method comprises administering to the subject a therapeutically effective amount of a polynucleotide agent which is substantially complementary to a nucleotide sequence of human miR-132, thereby treating the lipid related disorder in the subject.

What is claimed is: 
     
         1 . A method of treating a nonalcoholic steatohepatitis (NASH) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polynucleotide, which is substantially complementary to a nucleotide sequence of human miR-132, wherein said polynucleotide is at least 12-30 nucleotides in length, thereby treating the NASH. 
     
     
         2 . The method of  claim 1 , wherein said polynucleotide comprises the nucleic acid sequence as set forth in SEQ ID NO: 8 or at least 15 consecutive bases thereof. 
     
     
         3 . The method of  claim 2 , wherein said polynucleotide comprises the nucleic acid sequence as set forth in SEQ ID NO: 7 or SEQ ID NO: 10. 
     
     
         4 . The method of  claim 1 , wherein said polynucleotide comprises a modified internucleotide linkage selected from the group consisting of phosphoroamidate, phosphorothiate, phosphorodithioate, boranophosphate, alkylphosphonate and methylinemethylimino. 
     
     
         5 . The method of  claim 1 , wherein said polynucleotide comprises a modified nucleic acid unit selected from the group consisting of locked nucleic acid unit, 2′-O-alkyl ribonucleic acid unit, 2′amine ribonucleic acid unit, peptide nucleic acid unit, 2′fluoro-ribo nucleic acid unit, morpholino nucleic acid unit, cyclohexane nucleic acid unit and a tricyclonucleic acid unit. 
     
     
         6 . The method of  claim 1 , wherein said nucleic acid unit comprises a modified nucleic acid unit selected from the group consisting of locked nucleic acid unit, 2′-O-methyl ribonucleic acid unit, and 2′O-methoxy-ethyl ribonucleic acid unit. 
     
     
         7 . The method of  claim 1 , wherein said polynucleotide comprises a locked nucleic acid, a 2′-O-methyl ribonucleic acid, or a mixed nucleic acid-locked nucleic acid. 
     
     
         8 . The method of  claim 1 , wherein each of the nucleotides of said polynucleotide is a locked nucleic acid. 
     
     
         9 . The method of  claim 1 , wherein said administering is effected once per day. 
     
     
         10 . The method of  claim 1 , wherein said administering is effected once a week. 
     
     
         11 . The method of  claim 1 , wherein a dose of said polynucleotide is between 1 μg/kg body weight-100 mg/kg body weight per administration. 
     
     
         12 . The method of  claim 1 , wherein the subject does not have an eye disease. 
     
     
         13 . The method of  claim 1 , wherein the subject does not have a neurodegenerative disease. 
     
     
         14 . The method of  claim 1 , wherein the subject does not have cancer. 
     
     
         15 . A method of treating a nonalcoholic fatty liver disease (NAFLD) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a polynucleotide, which is substantially complementary to a nucleotide sequence of human miR-132, wherein said polynucleotide is at least 12-30 nucleotides in length, thereby treating the NAFLD. 
     
     
         16 . The method of  claim 15 , wherein said polynucleotide comprises the nucleic acid sequence as set forth in SEQ ID NO: 8 or at least 15 consecutive bases thereof. 
     
     
         17 . The method of  claim 16 , wherein said polynucleotide comprises the nucleic acid sequence as set forth in SEQ ID NO: 7 or SEQ ID NO: 10. 
     
     
         18 . The method of  claim 15 , wherein said polynucleotide comprises a modified internucleotide linkage selected from the group consisting of phosphoroamidate, phosphorothiate, phosphorodithioate, boranophosphate, alkylphosphonate and methylinemethylimino. 
     
     
         19 . The method of  claim 15 , wherein said polynucleotide comprises a modified nucleic acid unit selected from the group consisting of locked nucleic acid unit, 2′-O-alkyl ribonucleic acid unit, 2′amine ribonucleic acid unit, peptide nucleic acid unit, 2′fluoro-ribo nucleic acid unit, morpholino nucleic acid unit, cyclohexane nucleic acid unit and a tricyclonucleic acid unit. 
     
     
         20 . The method of  claim 15 , wherein said nucleic acid unit comprises a modified nucleic acid unit selected from the group consisting of locked nucleic acid unit, 2′-O-methyl ribonucleic acid unit, and 2′O-methoxy-ethyl ribonucleic acid unit. 
     
     
         21 . The method of  claim 15 , wherein said polynucleotide comprises a locked nucleic acid, a 2′-O-methyl ribonucleic acid, or a mixed nucleic acid-locked nucleic acid. 
     
     
         22 . The method of  claim 15 , wherein each of the nucleotides of said polynucleotide is a locked nucleic acid. 
     
     
         23 . The method of  claim 15 , wherein said administering is effected once per day or once a week. 
     
     
         24 . The method of  claim 15 , wherein a dose of said polynucleotide is between 1 μg/kg body weight-100 mg/kg body weight per administration. 
     
     
         25 . The method of  claim 15 , wherein the subject does not have an eye disease, a neurodegenerative disease and/or cancer.