Gene therapy for spinal cord disorders

Abstract

This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.

1 - 4 . (canceled) 
     
     
         5 . A method to treat a motor neuron disorder in a subject, comprising administering a recombinant neurotropic viral vector comprising a therapeutic transgene to at least one region of the deep cerebellar nuclei region of the brain under conditions that favor expression of the transgene in a motor neuron distal to the site of administration, wherein the transgene product is delivered in a therapeutically effective amount to at least one subdivision of the spinal cord and/or at least one division of the brainstem, wherein said neurotropic viral vector is an adeno-associated viral vector comprising an AAV8 serotype capsid. 
     
     
         6 - 8 . (canceled) 
     
     
         9 . The method of  claim 5 , wherein said region of the deep cerebellar nuclei region of the brain is selected from the group consisting of the medial region, interposed region and the lateral region. 
     
     
         10 . The method of  claim 5 , wherein said delivery is bilateral. 
     
     
         11 . The method of  claim 5 , wherein said spinal cord subdivision is selected from the group consisting of the cervical subdivision, the thoracic subdivision, the lumbar subdivision, and the sacral subdivision. 
     
     
         12 . The method of  claim 5 , wherein said transgene product is delivered to all subdivisions of the spinal cord. 
     
     
         13 . The method of  claim 5 , wherein the administration comprises multiple administrations. 
     
     
         14 . The method of  claim 5 , wherein said transgene is selected from the group consisting of insulin growth factor-1 (IGF-1), calbindin D28, paralbumin, HIF1-alpha, SIRT-2, VEGF, SMN-1, SMN-2 and CNTF (Ciliary neurotrophic factor). 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 5 , wherein said subject is a human patient. 
     
     
         17 . The method of  claim 5 , wherein said transgene expresses a therapeutic amount of a protein selected from the group consisting of insulin growth factor-1 (IGF-1), EPO (erythropoietin), CBP (cAMP response element binding protein [CREB] binding protein), calbindin D28, paralbumin, HIF1-alpha, SIRT-2, VEGF, SMN-1, SMN-2 and CNTF (Ciliary neurotrophic factor). 
     
     
         18 . The method of  claim 5 , wherein the AAV vector comprises an AAV2 ITR or an AAV8 ITR. 
     
     
         19 . The method of  claim 13 , wherein at least one of the multiple administrations is bilateral.