Peripherally delivered glutamic acid decarboxylase gene therapy for spinal cord injury pain

Abstract

The invention provides a vector, preferably a herpes simplex virus (HSV) vector, comprising a polynucleotide sequence encoding a glutamic acid decarboxylase (GAD) protein. The invention also provides a stock of such vectors and a pharmaceutical composition comprising such vectors. The invention further provides a method of treating pain, such as spinal cord injury pain, in a mammal comprising administering to a mammal a vector comprising a nucleotide sequence encoding a glutamic acid decarboxylase (GAD) protein in an amount effective to treat spinal cord injury pain.

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         13 . A method of treating spinal cord injury pain or peripheral neuropathic pain in a mammal comprising: administering to a mammal experiencing spinal cord injury pain or peripheral neuropathic pain a vector comprising a nucleotide sequence encoding a glutamic acid decarboxylase (GAD) protein in an amount effective to treat spinal cord injury pain or peripheral neuropathic pain.  
     
     
         14 . The method of  claim 13 , wherein the vector is a viral vector.  
     
     
         15 . The method of  claim 14 , wherein the viral vector is selected from the group consisting of: adenovirus vectors, herpes simplex virus (HSV) vectors, parvovirus vectors, and lentivirus vectors.  
     
     
         16 . The method of  claim 15 , wherein the viral vector is a non-amplicon HSV vector.  
     
     
         17 . The method of  claim 13 , wherein the vector is a non-viral vector.  
     
     
         18 . The method of  claim 13 , wherein the GAD protein is GAD67.  
     
     
         19 . The method of  claim 13 , wherein the polynucleotide sequence encoding the GAD protein is operably linked to a promoter.  
     
     
         20 . The method of  claim 19 , wherein the promoter is a human cytomegalovirus immediate early promoter (HCMV IEp).  
     
     
         21 . The method of  claim 16 , wherein the vector is deficient for at least one essential HSV gene.  
     
     
         22 . The method of  claim 21 , wherein the essential HSV gene is an early, immediate-early, or late HSV gene.  
     
     
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         25 . The method of  claim 16 , wherein the non-amplicon HSV vector is replication deficient.  
     
     
         26 . The method of  claim 13 , wherein the vector is peripherally administered.  
     
     
         27 . The method of  claim 25 , wherein the vector is administered to an appendage.  
     
     
         28 . The method of  claim 26 , wherein the appendage is below a level of spinal cord injury.  
     
     
         29 . The method of  claim 13 , wherein the mammal is a human.  
     
     
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