Methods and compositions for treatment of myotonia
View Patent ↗The present invention provides methods and compositions for the treatment of diseases associated with aberrant microsatellite expansions. Methods of the present invention comprise the use of recombinant adeno-associated virus vectors containing a transgene encoding at least one muscleblind protein. The present invention also provides an animal model for a disease associated with aberrant microsatellite expansion.
1. A method of treating myotonia in the muscle of a subject suffering from myotonia, comprising intramuscular injection of a recombinant adeno-associated virus (rAAV) vector comprising a promoter operably linked to a nucleic acid encoding a MBNL1 protein, wherein expression of the protein results in reducing myotonia in the muscle of the subject.
2. The method of claim 1 , wherein treating comprises reducing the mis-splicing of the Clcn1 skeletal muscle chloride channel gene.
3. The method of claim 1 , wherein treating comprises reducing the mis-splicing of the Amyloid beta (A4) precursor protein (APP) gene.
4. The method of claim 1 , wherein treating comprises reducing the mis-splicing of the NMDA receptor NR1 (GRIN1) gene.
5. The method of claim 1 , wherein treating comprises reducing the mis-splicing of the Microtubule-associated protein tau (MAPT) gene.
6. The method of claim 1 , wherein treating comprises reducing the mis-splicing of the TNNT2 (cTNT) gene.
7. The method of claim 1 , wherein the subject is human.
8. The method of claim 1 , wherein the subject has RNA inclusions in neuronal cells.