Therapeutic Targeting of a microRNA to Treat Duchenne Muscular Dystrophy

Abstract

Methods of treating Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), comprising administering an inhibitory nucleic acid that targets miR-128.

1 . A method of treating, increasing muscle mass in, or reducing or delaying muscle loss in, a subject who has Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD), the method comprising administering to the subject a therapeutically effective amount of an inhibitory nucleic acid that is complementary to all or part of any of SEQ ID NOs: 1-6. 
     
     
         2 . (canceled) 
     
     
         3 . A method of treating, or reducing risk of developing, dilated cardiomyopathy (DCM) in a subject, optionally wherein the subject has Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD), the method comprising administering to the subject an inhibitory nucleic acid sequence that is complementary to all or part of any of SEQ ID NOs:1-6. 
     
     
         4 . The method of  claim 1 , wherein the inhibitory nucleic acid is complementary to all or part of SEQ ID NO:2. 
     
     
         5 . The method of  claim 1 , wherein the inhibitory nucleic acid is complementary to at least nucleotides 2-7 (5′-CACAGU-3′) of SEQ ID NO:3. 
     
     
         6 . The method of  claim 1 , wherein the inhibitory nucleic acid is an antisense oligonucleotide. 
     
     
         7 . The method of  claim 6 , wherein the antisense oligonucleotide comprises a sequence that is complementary to SEQ ID NO:3. 
     
     
         8 . The method of  claim 6 , wherein the antisense oligonucleotide is an antagomir. 
     
     
         9 . The method of  claim 1 , wherein the inhibitory nucleic acid is an interfering RNA. 
     
     
         10 . The method of  claim 9 , wherein the interfering RNA is a small hairpin RNA (shRNA) or small interfering RNA (siRNA). 
     
     
         11 . The method of  claim 1 , wherein the inhibitory nucleic acid sequence inhibits post-transcriptional processing of SEQ ID NO:1 or 5. 
     
     
         12 . The method of  claim 1 , wherein the subject has DMD, and optionally wherein the method further comprises selecting a subject on the basis that they have DMD. 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 1 , wherein the inhibitory nucleic acid has at least one locked nucleotide, optionally wherein at least half of the nucleic acids are locked, or wherein all of the nucleic acids are locked. 
     
     
         15 . The method of  claim 1 , wherein the inhibitory nucleic acid has a phosphorothioate backbone. 
     
     
         16 . The method of  claim 1 , wherein the inhibitory nucleic acid is or comprises TTCACTGTG (SEQ ID NO:10) or GGTTCACTGTG (SEQ ID NO:11), 
     
     
         17 .- 18 . (canceled) 
     
     
         19 . The method of  claim 16 , wherein the backbone is a phosphorothioate backbone. 
     
     
         20 . The method of  claim 1 , wherein the inhibitory nucleic acid is or comprises +G*+G*+T*+T*C*A*C*+T*+G*+T*+G (SEQ ID NO:8). 
     
     
         21 . The method of  claim 20 , wherein the inhibitory nucleic acid is administered at a dose of 1-20 mg/kg. 
     
     
         22 . The method of  claim 21 , wherein the inhibitory nucleic acid is administered once or twice per month. 
     
     
         23 . An inhibitory nucleic acid, which is or comprises +G*+G*+T*+T*C*A*C*+T*+G*+T*+G (SEQ ID NO:8). 
     
     
         24 . A pharmaceutical composition comprising the inhibitory nucleic acid of  claim 23 . 
     
     
         25 .- 28 . (canceled)