Methods to treat pompe disease using a recombinant adeno-associated virus

Abstract

A method to prevent, inhibit or treat one or more symptoms associated with a disease of the central nervous system by intrathecally, intracerebroventricularly or endovascularly administering a rAAV encoding a gene product associated with the disease, e.g., a mammal in which the gene product is absent or present at a reduced level relative to a mammal without the disease.

What is claimed is: 
     
         1 . A method to inhibit or treat one or more symptoms of Pompe Disease in a mammal in need thereof, comprising:
 administering to a cisterna magna of the mammal in need thereof a composition comprising an amount of a recombinant adeno-associated virus (rAAV) 9 or rAAVrh10 vector comprising an open reading frame encoding acid maltase effective to inhibit or treat the one or more symptoms of Pompe Disease.   
     
     
         2 . The method of  claim 1  wherein the mammal is an immunocompetent adult. 
     
     
         3 . The method of  claim 1  wherein the mammal is a human. 
     
     
         4 . The method of  claim 1  wherein neurodegeneration is inhibited or treated by the administration. 
     
     
         5 . The method of  claim 1  wherein prior to administration of the composition the mammal is immunotolerized to acid maltase. 
     
     
         6 . The method of  claim 1  wherein the amount administered reduces glycosaminoglycans (GAG). 
     
     
         7 . The method of  claim 1  wherein rAAV9 vector is administered. 
     
     
         8 . The method of  claim 1  wherein rAAVrh10 vector is administered. 
     
     
         9 . A method to inhibit or treat one or more symptoms of Pompe Disease in a mammal in need thereof, comprising: administering to the mammal in need thereof an immune suppressant, and to a cisterna magna of the mammal a composition comprising an amount of a rAAV9 or rAAVrh10 vector comprising an open reading frame encoding acid maltase effective to inhibit or treat the one or more symptoms of Pompe Disease. 
     
     
         10 . The method of  claim 9  wherein the immune suppressant comprises cyclophosphamide, a glucocorticoid, cytostatic agents including an alkylating agent, an anti-metabolite, a cytotoxic antibiotic, an antibody, an agent active on immunophilin, a nitrogen mustard, nitrosourea, platinum compound, methotrexate, azathioprine, mercaptopurine, fluorouracil, dactinomycin, an anthracyclin e, mitomycin C, bleomycin, mithramycin, 1L-2 receptor-(CD25-) or CD3-directed antibodies, anti-IL-2 antibodies, ciclosporin, tacrolimus, sirolimus, IFN-beta, IFN-gamma, an opioid, or a TNF-alpha (tumor ecrosis factor-alpha) binding agent. 
     
     
         11 . The method of  claim 9  wherein the rAAV vector and the immune suppressant are co-administered or the immune suppressant is administered after the rAAV vector. 
     
     
         12 . The method of  claim 9  wherein the rAAV vector is a rAAV-9 vector. 
     
     
         13 . The method of  claim 9  wherein multiple doses of the composition comprising the rAAV9 or rAAVrh10 vector are administered. 
     
     
         14 . The method of  claim 9  wherein the rAAV vector is rAAVrh10 vector. 
     
     
         15 . The method of  claim 9  wherein the immune suppressant is administered before the rAAV9 or rAAVrh10 vector. 
     
     
         16 . The method of  claim 9  wherein the immune suppressant is systemically administered. 
     
     
         17 . The method of  claim 9  wherein the mammal is a human. 
     
     
         18 . The method of  claim 9  wherein the amount administered reduces glycosaminoglycans (GAG). 
     
     
         19 . A method to inhibit or treat one or more symptoms associated with a deficiency in acid maltase in a mammal, comprising: providing a mammal with a deficiency in acid maltase that is immunotolerized to acid maltase; and administering to a cisterna macro of the mammal a composition comprising an amount of a rAAV9 or rAAVrh10 vector comprising an open reading frame encoding acid maltase effective to inhibit or treat the one or more symptoms associated with the deficiency in acid maltase. 
     
     
         20 . The method of  claim 19  wherein multiple doses of the composition comprising the rAAV9 or rAAVrh10 vector are administered. 
     
     
         21 . The method of  claim 19  wherein rAAV9 vector is administered. 
     
     
         22 . The method of  claim 19  wherein rAAVrh10 vector is administered. 
     
     
         23 . The method of  claim 19  wherein the mammal is a human. 
     
     
         24 . The method of  claim 19  wherein the amount administered reduces glycosaminoglycans (GAG).