Exon skipping oligomer conjugates for muscular dystrophy
Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 52 skipping are described.
1. A method for treating Duchenne muscular dystrophy (DMD) in a subject in need thereof wherein the subject has a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the antisense oligomer is of Formula (VIIA):
3. A method of restoring an mRNA reading frame to induce dystrophin production in a subject having a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
4. A method for treating Duchenne muscular dystrophy (DMD) in a subject in need thereof wherein the subject has a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject a pharmaceutical composition comprising an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
5. A method of restoring an mRNA reading frame to induce dystrophin production in a subject having a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject a pharmaceutical composition comprising an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
6. A method of excluding exon 52 from dystrophin pre-mRNA during mRNA processing in a subject having a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject a pharmaceutical composition comprising an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
7. A method of binding exon 52 of dystrophin pre-mRNA in a subject having a mutation of the dystrophin gene that is amenable to exon 52 skipping, the method comprising administering to the subject a pharmaceutical composition comprising an antisense oligomer of Formula (VIIA):
or a pharmaceutically acceptable salt thereof.
8. The method of claim 1 , wherein the antisense oligomer is administered weekly.
9. The method of claim 1 , wherein the antisense oligomer is administered biweekly.
10. The method of claim 1 , wherein the antisense oligomer is administered every third week.
11. The method of claim 1 , wherein the antisense oligomer is administered monthly.
12. The method of claim 1 , wherein the antisense oligomer is administered at a dose selected from about 30 mg/kg, about 40 mg/kg, about 60 mg/kg, about 80 mg/kg, and about 160 mg/kg.
13. The method of claim 3 , wherein the antisense oligomer is administered weekly.
14. The method of claim 3 , wherein the antisense oligomer is administered biweekly.
15. The method of claim 3 , wherein the antisense oligomer is administered every third week.
16. The method of claim 3 , wherein the antisense oligomer is administered monthly.
17. The method of claim 3 , wherein the antisense oligomer is administered at a dose selected from about 30 mg/kg, about 40 mg/kg, about 60 mg/kg, about 80 mg/kg, and about 160 mg/kg.