Micrornas in neurodegenerative disorders

Abstract

Provided herein are methods of treating a neurodegenerative disorder such as Amyotrophic Lateral Sclerosis (ALS) or Multiple Sclerosis (MS) that include administering to a subject at least one inhibitory nucleic acid that decreases the level or activity of microRNA has-miR-155.

1 . A method of treating a subject having Alzheimer's Disease (AD), the method comprising identifying a subject who has AD and administering to the subject having AD at least one inhibitory nucleic acid comprising a sequence that is complementary to mature microRNA hsa-miR-155 having the sequence of SEQ ID NO:58, wherein the inhibitory nucleic acid reduces a level or activity of hsa-miR-155 in monocytes of the subject. 
     
     
         2 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is an antisense oligonucleotide. 
     
     
         3 . The method of  claim 1 , wherein the inhibitory nucleic acid comprises a sequence that is complementary to at least five nucleotides of the seed sequence of mature microRNA hsa-miR-155 
     
     
         4 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is administered intravenously or intrathecally. 
     
     
         5 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is administered by injection into the cerebrospinal fluid. 
     
     
         6 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is complexed with one or more cationic polymers or cationic lipids. 
     
     
         7 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is complementary to a contiguous sequence of at least 12 nucleotides present in hsa-miR-155. 
     
     
         8 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is complementary to a contiguous sequence of at least 14 nucleotides present in hsa-miR-155. 
     
     
         9 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid is complementary to a contiguous sequence of at least 15 nucleotides present in hsa-miR-155. 
     
     
         10 . The method of  claim 1 , wherein the at least one inhibitory nucleic acid comprises at least one locked nucleic acid (LNA). 
     
     
         11 . The method of  claim 1 , wherein the subject who has AD is human.