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 - 9 . (canceled) 
     
     
         10 . A method of treating a neurological disease in a patient in need thereof comprising intrathecal delivery of a rAAV9 and a non-ionic, low-osmolar contrast agent to the patient, wherein the rAAV9 comprises a self-complementary genome including a therapeutic polynucleotide and wherein
 a) the neurological disease is CLN1 disease and the therapeutic polynucleotide is a CLN1 polynucleotide,   b) the neurological disease is CLN2 disease and the therapeutic polynucleotide is a CLN2 polynucleotide,   c) the neurological disease is CLN3 disease and the therapeutic polynucleotide is a CLN3 polynucleotide,   d) the neurological disease is CLN4 disease and the therapeutic polynucleotide is a CLN4 polynucleotide,   e) the neurological disease is CLN5 disease and the therapeutic polynucleotide is a CLN5 polynucleotide,   f) the neurological disease is CLN6 disease and the therapeutic polynucleotide is a CLN6 polynucleotide, or   g) the neurological disease is CLN8 disease and the therapeutic polynucleotide is a CLN8 polynucleotide.   
     
     
         11 - 20 . (canceled) 
     
     
         21 . The method of  claim 10  wherein the non-ionic, low-osmolar contrast agent is iobitridol, iohexol, iomeprol, iopamidol, iopentol, iopromide, ioversol or ioxilan. 
     
     
         22 . The method of  claim 21  wherein the non-ionic, low-osmolar contrast agent is iohexol. 
     
     
         23 . The method of  claim 10  wherein the patient is put in the Trendelenberg position after intrathecal delivery of the rAAV9.