Micrornas in neurodegenerative disorders
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 hsa-miR-155.
1. A method of increasing the longevity of a subject having amyotrophic lateral sclerosis (ALS), the method comprising identifying a subject who has ALS, and administering to the subject having ALS at least one inhibitory nucleic acid comprising a sequence that is complementary to a contiguous sequence of at least 12 nucleotides present in mature microRNA hsa-miR-155 having the sequence of SEQ ID NO:58, wherein at least five of said at least 12 nucleotides are within the seed sequence of mature microRNA hsa-miR-155, wherein the inhibitory nucleic acid comprises at least one locked nucleotide, wherein the inhibitory nucleic acid reduces level or activity of hsa-miR-155 in monocytes of the subject, and wherein the inhibitory nucleic acid is administered intravenously or intrathecally.
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 is administered via intrathecal injection.
4. The method of claim 1 , wherein the at least one inhibitory nucleic acid is complexed with one or more cationic polymers and/or cationic lipids.
5. 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.
6. 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.
7. The method of claim 1 , wherein the at least one inhibitory nucleic acid comprises at least one locked nucleic acid (LNA).
8. The method of claim 5 , wherein the at least one inhibitory nucleic acid comprises at least one locked nucleic acid (LNA).
9. The method of claim 6 , wherein the at least one inhibitory nucleic acid comprises at least one locked nucleic acid (LNA).
10. The method of claim 1 , wherein the subject has increased levels of hsa-miR-155 in the subject's monocytes.
11. The method of claim 1 , wherein the subject is human.