Compositions and methods for modulation of smn2 splicing in a subject

Abstract

Disclosed herein are compounds, compositions and methods for modulating splicing of SMN2 mRNA in a subject. Also provided are uses of disclosed compounds and compositions in the manufacture of a medicament for treatment of diseases and disorders, including spinal muscular atrophy.

1 . A method of treating a human patient having spinal muscular atrophy comprising administering to the human patient at least one dose of an antisense compound comprising an antisense oligonucleotide complementary to intron 7 of a nucleic acid encoding human SMN2 pre-mRNA, wherein the antisense compound is administered into the cerebrospinal fluid at a dose of 0.1 to 20 milligrams; and thereby ameliorating at least one symptom of spinal muscular atrophy in the human patient. 
     
     
         2 - 11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the dose is from 1 to 20 milligrams. 
     
     
         13 . The method of  claim 1 , wherein the dose is from 1 to 15 milligrams. 
     
     
         14 . The method of  claim 1 , wherein the dose is from 1 to 10 milligrams. 
     
     
         15 . The method of  claim 1 , wherein the dose is from 1 to 5 milligrams. 
     
     
         16 . The method of  claim 1 , wherein the dose is from 3 to 20 milligrams. 
     
     
         17 . The method of  claim 1 , wherein the dose is from 3 to 15 milligrams. 
     
     
         18 - 235 . (canceled) 
     
     
         236 . An antisense compound comprising an antisense oligonucleotide complementary to intron 7 of a nucleic acid encoding human SMN2, for use in a method according to  claim 1 . 
     
     
         237 . The antisense compound according to  claim 236 , for use in treating a disease or condition associated with survival motor neuron 1 (SMN1). 
     
     
         238 - 239 . (canceled) 
     
     
         240 . Use of an antisense compound comprising an antisense oligonucleotide complementary to intron 7 of a nucleic acid encoding human SMN2 in the manufacture of a medicament for use in a method according to  claim 1 .