Compositions for modulating SOD-1 expression
Disclosed herein are antisense compounds and methods for decreasing SOD-1 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate SOD-1 associated diseases, disorders, and conditions. Such SOD-1 associated diseases include amyotrophic sclerosis (ALS).
1. A method for treating or preventing a superoxide dismutase 1 (SOD1) associated neurodegenerative disorder in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an antisense compound according to the following formula:
mCes Aeo Ges Geo Aes Tds Ads mCds Ads Tds Tds Tds mCds Tds Ads mCeo Aes Geo mCes Te (nucleobase sequence of SEQ ID NO:725); wherein,
A=an adenine,
mC=a 5-methylcytosine
G=a guanine,
T=a thymine,
e=a 2′-O-methoxyethylribose modified sugar,
d=a 2′-deoxyribose sugar,
s=a phosphorothioate internucleoside linkage, and
o=a phosphodiester internucleoside linkage;
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the SOD1 associated neurodegenerative disorder is SOD1 associated amyotrophic lateral sclerosis (ALS).
3. The method of claim 1 , wherein the antisense compound or the pharmaceutically acceptable salt is administered intrathecally.
4. The method of claim 1 , wherein the pharmaceutically acceptable salt is a sodium salt.
5. The method of claim 1 , wherein the method comprises administering to the human subject a therapeutically effective amount of the antisense compound.
6. The method of claim 5 , wherein the antisense compound is administered intrathecally.
7. A method for treating or preventing a superoxide dismutase 1 (SOD1) associated neurodegenerative disorder in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an antisense compound according to the following formula:
or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein the SOD1 associated neurodegenerative disorder is SOD1 associated amyotrophic lateral sclerosis (ALS).
9. The method of claim 7 , wherein the antisense compound or the pharmaceutically acceptable salt thereof is administered intrathecally.
10. The method of claim 7 , wherein the pharmaceutically acceptable salt is a sodium salt.
11. The method of claim 7 , wherein the method comprises administering to the human subject a therapeutically effective amount of the antisense compound.
12. The method of claim 11 , wherein the antisense compound is administered intrathecally.
13. A method of reducing superoxide dismutase 1 (SOD1) expression in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an antisense compound according to the following formula:
mCes Aeo Ges Geo Aes Tds Ads mCds Ads Tds Tds Tds mCds Tds Ads mCeo Aes Geo mCes Te (nucleobase sequence of SEQ ID NO:725); wherein,
A=an adenine,
mC=a 5-methylcytosine
G=a guanine,
T=a thymine,
e=a 2′-O-methoxyethylribose modified sugar,
d=a 2′-deoxyribose sugar,
s=a phosphorothioate internucleoside linkage, and
o=a phosphodiester internucleoside linkage;
or a pharmaceutically acceptable salt thereof.
14. A method of reducing superoxide dismutase 1 (SOD1) expression in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of an antisense compound according to the following formula:
or a pharmaceutically acceptable salt thereof.
15. The method of claim 13 , wherein the human subject has SOD1 associated amyotrophic lateral sclerosis (ALS).
16. The method of claim 13 , wherein the antisense compound or the pharmaceutically acceptable salt thereof is administered intrathecally.
17. The method of claim 13 , wherein the pharmaceutically acceptable salt is a sodium salt.
18. The method of claim 13 , wherein the method comprises administering to the human subject a therapeutically effective amount of the antisense compound.
19. The method of claim 13 , wherein the antisense compound is administered intrathecally.
20. The method of claim 14 , wherein the human subject has SOD1 associated amyotrophic lateral sclerosis (ALS).
21. The method of claim 14 , wherein the antisense compound or the pharmaceutically acceptable salt thereof is administered intrathecally.
22. The method of claim 14 , wherein the pharmaceutically acceptable salt is a sodium salt.
23. The method of claim 14 , wherein the method comprises administering to the human subject a therapeutically effective amount of the antisense compound.
24. The method of claim 14 , wherein the antisense compound is administered intrathecally.
25. The method of claim 1 , wherein the method comprises treating SOD1 associated amyotrophic lateral sclerosis (ALS) in the human subject.
26. The method of claim 25 , wherein the antisense compound or the pharmaceutically acceptable salt thereof is administered intrathecally.
27. The method of claim 7 , wherein the method comprises treating SOD1 associated amyotrophic lateral sclerosis (ALS) in the human subject.
28. The method of claim 27 , wherein the antisense compound or the pharmaceutically acceptable salt thereof is administered intrathecally.