Intrathecal delivery of recombinant adeno-associated virus 9

Abstract

The present invention relates to Adeno-associated virus type 9 methods and materials useful for intrathecal delivery of polynucleotides. Use of the methods and materials is indicated, for example, for treatment of lower motor neuron diseases such as SMA and ALS as well as Pompe disease and lysosomal storage disorders. It is disclosed that administration of a non-ionic, low-osmolar contrast agent, together with a rAA9 vector for the expression of Survival Motor Neuron protein, improves the survival of SMN mutant mice as compared to the administration of the expression vector alone.

1 - 23 . (canceled) 
     
     
         24 . A composition comprising: (a) a recombinant AAV9 (rAAV9) comprising a self-complementary genome comprising a CLN6 gene; and (b) a transduction agent. 
     
     
         25 . The composition of  claim 24 , wherein the transduction agent is a contrast agent. 
     
     
         26 . The composition of  claim 25 , wherein the contrast agent is a non-ionic, low-osmolar contrast agent. 
     
     
         27 . The composition of  claim 26 , wherein the non-ionic, low-osmolar contrast agent is selected from the group consisting of iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, and combinations thereof. 
     
     
         28 . The composition of  claim 26 , wherein the non-ionic, low-osmolar contrast agent is iohexol. 
     
     
         29 . A method of treating a CLN6 disease in a patient in need thereof comprising, administering to the patient by intrathecal delivery an effective amount of a composition of  claim 24 . 
     
     
         30 . The method of  claim 29 , further comprising placing the patient in the Trendelenberg position after intrathecal delivery of the composition. 
     
     
         31 . The method of  claim 29 , wherein the transduction agent is a contrast agent. 
     
     
         32 . The method of  claim 31 , wherein the contrast agent is a non-ionic, low-osmolar contrast agent. 
     
     
         33 . The method of  claim 32 , wherein the non-ionic, low-osmolar contrast agent is selected from the group consisting of iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, and combinations thereof. 
     
     
         34 . The method of  claim 32 , wherein the non-ionic, low-osmolar contrast agent is iohexol.