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 rAAV9 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 . A method of treating a CLN2 disease in a patient in need thereof, comprising delivering intrathecally to the patient a composition comprising a combination of a recombinant AAV9 (rAAV9) and a non-ionic, low-osmolar contrast agent, wherein the rAAV9 comprises an rAAV9 genome comprising a CLN2 gene. 
     
     
         2 . The method according to  claim 1 , wherein the rAAV9 genome is a self-complementary genome. 
     
     
         3 . The method of  claim 1 , wherein the rAAV9 genome is a single-stranded genome. 
     
     
         4 . The method of  claim 1 , wherein the non-ionic, low-osmolar contrast agent is iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol, ioxilan, or a combination thereof. 
     
     
         5 . The method according to  claim 1 , wherein the non-ionic, low-osmolar contrast agent is iohexol. 
     
     
         6 . The method of  claim 1 , wherein the composition is formed by mixing the rAAV9 and the non-ionic, low-osmolar contrast agent prior to delivering intrathecally to the patient. 
     
     
         7 . The method of  claim 1 , wherein the combination is delivered as sequential administrations. 
     
     
         8 . The method of  claim 1 , wherein delivering intrathecally comprises delivery into the space under the arachnoid membrane of the brain or spinal cord. 
     
     
         9 . The method according to  claim 1  wherein the patient is a human.