Compositions and Methods for Treating Diseases

Abstract

The present invention provides compositions and methods of use pertaining to rAAV-mediated delivery of therapeutically effective molecules for treatment of diseases such as Pompe disease. These compositions in combination with various routes and methods of administration result in targeted expression of therapeutic molecules in specific organs, tissues and cells.

1 . A method of improving impaired neuromuscular junction integrity, comprising administering, to a subject with impaired neuromuscular junction integrity, an effective amount of a composition comprising a rAAV 2/9 vector, wherein the rAAV2/9 vector comprises a heterologous nucleic acid molecule operably linked to a promoter, and the therapeutic composition is administered to the subject via intramuscular, intrathoracic, intraspinal, intrathecal, or intravenous injection. 
     
     
         2 . The method according to  claim 1 , wherein the heterologous nucleic acid molecule encodes acid α-glucosidase (GAA). 
     
     
         3 . The method according to  claim 1 , wherein the promoter is a cytomegalovirus (CMV) promoter or a desmin (DES) promoter. 
     
     
         4 . The method according to  claim 1 , wherein the promoter is a desmin (DES) promoter. 
     
     
         5 . The method according to  claim 1 , wherein the subject has impaired neuromuscular caused by a neuromuscular disease. 
     
     
         6 . The method according to  claim 1 , wherein the subject has impaired neuromuscular caused by a disease selected from the group consisting of Pompe disease, amyotrophic lateral sclerosis, spinal muscular atrophy, multiple sclerosis, glycogen storage disease type 1a, limb Girdle muscular dystrophy, Barth syndrome, and myasthenia gravis. 
     
     
         7 . The method according to  claim 1 , wherein the subject is a human. 
     
     
         8 . A method of treating a neuromuscular disease, comprising administering, to a subject in need of such treatment, an effective amount of a composition comprising a rAAV 2/9 vector, wherein the rAAV2/9 vector comprises a heterologous nucleic acid molecule operably linked to a promoter, and the therapeutic composition is administered to the subject via intramuscular, intrathoracic, intraspinal, intrathecal, or intravenous injection. 
     
     
         9 . The method according to  claim 8 , wherein the neuromuscular disease is selected from the group consisting of Pompe disease, amyotrophic lateral sclerosis, spinal muscular atrophy, multiple sclerosis, glycogen storage disease type 1a, limb Girdle muscular dystrophy, Barth syndrome, and myasthenia gravis 
     
     
         10 . The method according to  claim 9 , wherein the neuromuscular disease is Pompe disease. 
     
     
         11 . The method according to  claim 8 , wherein the heterologous nucleic acid molecule encodes acid α-glucosidase (GAA). 
     
     
         12 . The method according to  claim 8 , wherein the promoter is a cytomegalovirus (CMV) promoter or a desmin (DES) promoter. 
     
     
         13 . The method according to  claim 12 , wherein the promoter is a desmin (DES) promoter. 
     
     
         14 . The method according to  claim 8 , wherein the subject is a human. 
     
     
         15 . A method of improving impaired neuromuscular junction integrity and/or for treatment a neuromuscular disease, comprising administering to a subject an effective amount of a composition comprising a rAAV vector, wherein the rAAV vector comprises a heterologous nucleic acid molecule operably linked to a promoter, wherein the subject has impaired neuromuscular junction integrity and/or a neuromuscular disease and the subject does not have Pompe disease. 
     
     
         16 . The method according to  claim 15 , wherein the rAAV vector is selected from a rAAV2/1, rAAV2/8, or rAAV2/9 vector. 
     
     
         17 . The method according to  claim 15 , wherein the therapeutic composition is administered to the subject via intramuscular, intrathoracic, intraspinal, or intravenous injection. 
     
     
         18 . The method according to  claim 15 , wherein the promoter is a cytomegalovirus (CMV) promoter or a desmin (DES) promoter. 
     
     
         19 . The method according to  claim 15 , wherein the subject has a neuromuscular disease selected from the group consisting of amyotrophic lateral sclerosis, spinal muscular atrophy, multiple sclerosis, glycogen storage disease type 1a, limb Girdle muscular dystrophy, Barth syndrome, and myasthenia gravis. 
     
     
         20 . The method according to  claim 15 , wherein the subject is a human.