Antisense modulation of superoxide dismutase 1, soluble expression
View Patent ↗Antisense compounds, compositions and methods are provided for modulating the expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using these compounds for modulation of superoxide dismutase 1, soluble expression and for treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.
1. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering to the cerebrospinal fluid of a subject in need thereof a therapeutically or prophylactically effective amount of a composition comprising:
a modified oligonucleotide consisting of 12 to 30 linked nucleosides targeted to SOD-1,
wherein the modified oligonucleotide is specifically hybridizable to the coding region of SOD-1, and
a pharmaceutically acceptable diluent or carrier.
2. The method of claim 1 , wherein administering is intrathecal administration.
3. The method of claim 1 , wherein administering is intraventricular administration.
4. The method of claim 1 , wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage.
5. The method of claim 1 , wherein at least one nucleoside comprises a modified sugar.
6. The method of claim 5 , wherein the modified sugar is a 2′-O-methoxyethyl.
7. The method of claim 1 , wherein at least one nucleoside comprises a modified nucleobase.
8. The method of claim 7 , wherein the modified nucleobase is a 5-methylcytosine.
9. The method of claim 1 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is position between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
10. The method of claim 9 , wherein the modified oligonucleotide comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides;
a 3′ wing segment consisting of five linked nucleosides;
wherein the gap segment is position between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar; wherein each cytosine is a 5′methylcytosine, and wherein each internucleoside linkage is a phosphorothioate linkage.
11. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering to the cerebrospinal fluid of a subject in need thereof a therapeutically or prophylactically effective amount of a composition comprising:
a modified oligonucleotide consisting of 12 to 30 linked nucleosides targeted to SOD-1,
wherein the modified oligonucleotide is 100% complementary to the coding region of SOD-1, and
a pharmaceutically acceptable diluent or carrier.
12. The method of claim 11 , wherein administering is intrathecal administration.
13. The method of claim 11 , wherein administering is intraventricular administration.
14. The method of claim 11 , wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage.
15. The method of claim 11 , wherein at least one nucleoside comprises a modified sugar.
16. The method of claim 15 , wherein the modified sugar is a 2′-O-methoxyethyl.
17. The method of claim 11 , wherein at least one nucleoside comprises a modified nucleobase.
18. The method of claim 17 , wherein the modified nucleobase is a 5-methylcytosine.
19. The method of claim 11 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is position between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
20. The method of claim 19 , wherein the modified oligonucleotide comprises:
a gap segment consisting of ten linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides;
a 3′ wing segment consisting of five linked nucleosides;
wherein the gap segment is position between the 5′ wing segment and the 3′ wing segment, wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar; wherein each cytosine is a 5′methylcytosine, and wherein each internucleoside linkage is a phosphorothioate linkage.