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 inhibiting the expression of superoxide dismutase 1, soluble in at least one of brain and spinal cord, comprising intraventricularly or intrathecally administering to an animal a compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleobases, wherein the modified oligonucleotide is fully complementary to an equal number of consecutive nucleobases selected from 73-115 of SEQ ID NO:3 and inhibits the expression of superoxide dismutase 1, soluble.
2. The method of claim 1 wherein the modified oligonucleotide compound is an antisense oligonucleotide.
3. The method of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
4. The method of claim 3 wherein the modified internucleoside linkage is a phosphorothioate linkage.
5. The method of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar.
6. The method of claim 5 wherein the modified sugar is a 2′-O-methoxyethyl sugar.
7. The method of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
8. The method of claim 7 wherein the modified nucleobase is a 5-methylcytosine.
9. The method of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
10. The method of claim 1 wherein the animal is a human.
11. The method of claim 10 wherein the human has a neurodegenerative disorder.
12. The method of claim 11 wherein the neurodegenerative disorder is amyotrophic lateral sclerosis (ALS).
13. The method of claim 2 wherein the compound comprises a pharmaceutically acceptable salt.
14. The method of claim 1 wherein the compound is administered with a pharmaceutically acceptable carrier or diluent.
15. The method of claim 1 wherein the modified oligonucleotide consists of 20 linked nucleobases.
16. The method of claim 15 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 positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
17. The method of claim 16 wherein the modified oligonucleotide comprises:
a gap segment consisting often 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 positioned 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 internucleoside linkage of said modified oligonucleotide is a phosphorothioate linkage, and wherein each cytosine is a 5-methylcytosine.