Treatment of amyotrophic lateral sclerosis (als)

A modulatory polynucleotide comprising a sense strand sequence and an antisense strand sequence, wherein the sense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:

• 25, 22-24, or 26-46, and the antisense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:
• 7, 5-6, or 8-21, and wherein said sense strand sequence and antisense strand sequence comprise a region of complementarity of at least 17 nucleotides in length.

A method for treating amyotrophic lateral sclerosis (ALS) in a subject, the method comprising administering to the subject a therapeutically effective amount of an AAV viral genome comprising a nucleic acid sequence positioned between two inverted terminal repeats (ITRs), wherein said nucleic acid sequence encodes a modulatory polynucleotide, wherein the modulatory polynucleotide comprises a sense strand sequence and an antisense strand sequence, wherein the sense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:

• 25, 22-24, or 26-46, and the antisense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:
• 7, 5-6, or 8-21, wherein said sense strand sequence and antisense strand sequence comprise a region of complementarity of at least 17 nucleotides in length, thereby treating ALS in the subject.

A method for treating canine degenerative myelopathy (DM) in a subject administering to the subject a therapeutically effective amount of an AAV viral genome comprising a nucleic acid sequence positioned between two inverted terminal repeats (ITRs), wherein said nucleic acid sequence encodes a modulatory polynucleotide, wherein the modulatory polynucleotide comprises a sense strand sequence and an antisense strand sequence, wherein the sense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:

• 25, 22-24, or 26-46, and the antisense strand sequence comprises at least 20 consecutive nucleotides from any one of SEQ ID NOs:
• 7, 5-6, or 8-21, wherein said sense strand sequence and antisense strand sequence comprise a region of complementarity of at least 17 nucleotides in length, thereby treating canine DM in the subject.