Dynamin 2 inhibitor for the treatment of duchenne's muscular dystrophy

Abstract

The present disclosure relates to an inhibitor of Dynamin 2 or composition comprising the same for use in the treatment of Duchenne's muscular dystrophy.

1 . A method for the treatment of Duchenne's muscular dystrophy, wherein the method comprises the step of administering into a subject in need of such treatment a therapeutically efficient amount of a Dynamin 2 inhibitor. 
     
     
         2 . The method according to  claim 1 , wherein the dynamin 2 inhibitor is selected from the group consisting of an antibody directed against Dynamin 2, a nucleic acid molecule interfering specifically with Dynamin 2 expression, a nucleic acid or a nuclease engineered to target the DNM2 gene and to deliver nucleases using genome editing therapy, and a small molecule inhibiting the Dynamin 2 activity, expression or function. 
     
     
         3 . The method according to  claim 1 , wherein the dynamin 2 inhibitor is selected from the group consisting of an antibody directed against Dynamin 2 and a nucleic acid molecule interfering specifically with Dynamin 2 expression. 
     
     
         4 . The method according to  claim 1 , wherein the Dynamin 2 inhibitor is a RNAi, an antisense nucleic acid, a siRNA, a shRNA or a ribozyme interfering specifically with Dynamin 2 expression. 
     
     
         5 . The method according to  claim 1 , wherein the Dynamin 2 inhibitor is an antisense nucleotide inducing exon-skipping within a Dynamin 2 pre-mRNA. 
     
     
         6 - 7 . (canceled) 
     
     
         8 . The method according to  claim 1 , wherein the dynamin 2 inhibitor is a DNA, mRNA or a nuclease engineered to target the DNM2 gene and to deliver nucleases using genome editing therapy. 
     
     
         9 . The method according to  claim 1 , wherein the dynamin 2 inhibitor is administered in an amount sufficient to reduce the Dynamin 2 expression or the Dynamin 2 activity, expression or function in a level equal or less than the normal level. 
     
     
         10 . The method according to  claim 1 , wherein the Dynamin 2 inhibitor is an antisense nucleotide designed to specifically induce DNM2 exon 2 or exon 8 skipping. 
     
     
         11 . A method for identifying or screening molecules useful in the treatment of Duchenne's muscular dystrophy, comprising the steps of:
 a) providing or obtaining a candidate compound; and   b) determining whether said candidate compound inhibits the activity, function and/or expression of Dynamin 2, and   c) selecting said candidate compound if it inhibits the activity/expression/function of Dynamin 2.   
     
     
         12 . The method according to  claim 11 , said method further comprising the step of administering in vitro the selected molecule in a Duchenne's muscular dystrophy non-human animal model or a part thereof and analyzing the effect on the myopathy onset or progression. 
     
     
         13 . A pharmaceutical composition comprising an effective amount for the treatment of Duchenne's muscular dystrophy of an inhibitor of Dynamin 2, and a pharmaceutically acceptable carrier/excipient. 
     
     
         14 . The method according to  claim 1 , wherein the Dynamin 2 inhibitor is an antisense nucleic acid complementary to an mRNA sequence of Dynamin 2, or complementary to a part of a pre-mRNA encoding Dynamin 2.