Methods for modulating expression of C9ORF72 antisense transcript

1. A method of reducing the number of cells with C9ORF72 antisense RNA foci and/or reducing the number of C9ORF72 antisense RNA foci per cell in an animal identified as having C9ORF72 antisense RNA foci, comprising administering to the animal an effective amount of a compound comprising a modified oligonucleotide consisting of 20 to 30 linked nucleosides and comprising the nucleobase sequence of SEQ ID NO: 26, 46, or 47, wherein the modified oligonucleotide is at least 90% complementary to a C9ORF72 antisense transcript; and thereby reducing the number of cells with C9ORF72 antisense RNA foci and/or reducing the number of C9ORF72 antisense RNA foci per cell.

2. The method of claim 1 , wherein said amount is effective to reduce the level or expression of the C9ORF72 antisense transcript.

3. The method of claim 1 , wherein the animal has a C9ORF72 associated disease.

4. The method of claim 1 , wherein the modified oligonucleotide is 100% complementary to the C9ORF72 antisense transcript.

5. The method of claim 1 , wherein the C9ORF72 antisense transcript has the sequence of SEQ ID NO: 11.

6. The method of claim 3 , wherein the C9ORF72 associated disease is a C9ORF72 hexanucleotide repeat expansion associated disease.

7. The method of claim 3 , wherein the C9ORF72 associated disease is amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), corticalbasal degeneration syndrome (CBD), atypical Parkinsonian syndrome, or olivopontocerebellar degeneration (OPCD).

8. The method of claim 7 , wherein the amyotrophic lateral sclerosis (ALS) is familial ALS or sporadic ALS.

9. The method of claim 1 , wherein administering reduces the level of C9ORF72 antisense transcript associated RAN translation products.

10. The method of claim 9 , wherein the C9ORF72 antisense transcript associated RAN translation products are any of poly-(proline-alanine), poly-(proline-arginine), and poly-(proline-glycine).

11. The method of claim 1 , wherein the administering is parenteral administration.

12. The method of claim 11 , wherein the parenteral administration is any of injection or infusion.

13. The method of claim 11 , wherein the parenteral administration is any of intrathecal administration or intracerebroventricular administration.

14. The method of claim 3 , wherein at least one symptom of a C9ORF72 associated disease is slowed, ameliorated, or prevented.

15. The method of claim 1 , wherein at least one internucleoside linkage of the modified oligonucleotide is a modified internucleoside linkage.

16. The method of claim 15 , wherein the at least one modified internucleoside linkage is a phosphorothioate internucleoside linkage.

17. The method of claim 16 , wherein each modified internucleoside linkage is a phosphorothioate internucleoside linkage.

18. The method of claim 1 , wherein at least one nucleobase of the modified oligonucleotide is a modified nucleobase.

19. The method of claim 18 , wherein the modified nucleobase is a 5-methylcytosine.

20. The method of claim 1 , wherein at least one nucleoside of the modified oligonucleotide comprises a modified sugar.

21. The method of claim 20 , wherein the at least one modified sugar is a bicyclic sugar.

22. The method of claim 21 , wherein the bicyclic sugar comprises a chemical bridge between the 2′ and 4′ position of the sugar, wherein the chemical bridge is selected from: 4′-CH 2 -O-2′; 4′-CH(CH 3 )-O-2′; 4′-(CH 2 ) 2 -O-2′; and 4′-CH 2 -N(R)-O-2′ wherein R is, independently, H, C 1 -C 12 alkyl, or a protecting group.

23. The method of claim 20 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl group.

24. The method of claim 1 , wherein the modified oligonucleotide is a gapmer.

25. The method of claim 1 , wherein the modified oligonucleotide is a single-stranded oligonucleotide.

26. The method of claim 22 , wherein the chemical bridge is 4′-CH 2 -O-2′.

27. The method of claim 22 , wherein the chemical bridge is 4′-CH(CH 3 )-O-2′.