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.

1 - 23  (canceled) 
     
     
         24 . A pharmaceutical composition comprising a recombinant adeno-associated virus (rAAV) vector comprising a polynucleotide comprising nucleotides 980-3336 of SEQ ID NO:1, wherein the rAAV is present at a concentration of about 1×10 6  to about 1×10 14  vector genomes (vg) per milliliter (mL). 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the rAAV vector comprises a serotype 9 capsid. 
     
     
         26 . The pharmaceutical composition of  claim 24  wherein the rAAV vector comprises a self-complementary rAAV genome. 
     
     
         27 . The pharmaceutical composition of  claim 24 , comprising a pharmaceutically acceptable carrier. 
     
     
         28 . The pharmaceutical composition of  claim 24 , wherein the rAAV is present at a concentration of about 1×10 13  to about 1×10 14  vector genomes (vg) per milliliter (mL). 
     
     
         29 . A method of treating a neurological disease in a patient in need thereof comprising administering the pharmaceutical composition of  claim 28 . 
     
     
         30 . A method of treating a neurological disease in a patient in need thereof comprising administering the pharmaceutical composition of  claim 28 . 
     
     
         31 . The method of  claim 29 , wherein the rAAV is administered at a dose of from about 1×10 11  vg/kilogram (kg) body weight to about 1×10 16  vg/kg body weight. 
     
     
         32 . The method of  claim 30 , wherein the rAAV is administered at a dose of from about 1×10 11  vg/ kg body weight to about 1×10 16  vg/kg body weight. 
     
     
         33 . The method of  claim 31 , wherein the patient is a neonate and the rAAV is administered at a dose of from about 1×10 14  vg/kg body weight to about 3×10 14  vg/kg body weight. 
     
     
         34 . The method of  claim 32 , wherein the patient is a neonate and the rAAV is administered at a dose of from about 1×10 14  vg/kg body weight to about 3×10 14  vg/kg body weight. 
     
     
         35 . The method of  claim 33 , wherein the neurological disease is spinal muscular atrophy (SMA). 
     
     
         36 . The method of  claim 34 , wherein the neurological disease is spinal muscular atrophy (SMA).