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 human in need thereof, consisting of:
 administering to the human an amount of a recombinant adeno-associated virus (rAAV) vector having an AAV8, AAV9 or AAVrh10 capsid encapsidating a rAAV genome having an open reading frame encoding acid maltase that is effective to inhibit or treat the one or more symptoms of Pompe Disease in the human.   
     
     
         2 . The method of  claim 1  wherein the human is an immunocompetent adult. 
     
     
         3 . The method of  claim 1  wherein neurodegeneration is inhibited or treated by the administration. 
     
     
         4 . The method of  claim 1  wherein the amount administered reduces glycosaminoglycans (GAG). 
     
     
         5 . The method of  claim 1  wherein the vector having the AAV9 capsid is administered. 
     
     
         6 . The method of  claim 1  wherein the vector having AAVrh10 capsid is administered. 
     
     
         7 . The method of  claim 1  wherein the vector having the AAV8 capsid is administered. 
     
     
         8 . The method of  claim 1  wherein the rAAV vector is endovascularly administered. 
     
     
         9 . The method of  claim 1  wherein multiple doses of the rAAV vector are administered. 
     
     
         10 . A method to inhibit or treat one or more symptoms of Pompe Disease in a human in need thereof, consisting of:
 administering to the human an amount of a recombinant adeno-associated virus (rAAV) vector having an AAV8, AAV9 or AAVrh10 capsid encapsidating a rAAV genome having an open reading frame encoding acid maltase that is effective to inhibit or treat the one or more symptoms of Pompe Disease in the human and an effective amount of an immune suppressant.   
     
     
         11 . The method of  claim 10  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 anthracycline, mitomycin C, bleomycin, mithramycin, IL-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 necrosis factor-alpha) binding agent. 
 
     
     
         12 . The method of  claim 10  wherein the rAAV vector and the immune suppressant are co-administered. 
     
     
         13 . The method of  claim 10  wherein the immune suppressant is administered after the rAAV vector. 
     
     
         14 . The method of  claim 10  wherein the immune suppressant is administered before the rAAV vector. 
     
     
         15 . The method of  claim 10  wherein the immune suppressant is systemically administered. 
     
     
         16 . The method of  claim 10  wherein the vector having the AAV9 capsid is administered. 
     
     
         17 . The method of  claim 10  wherein the vector having the AAVrh10 capsid is administered. 
     
     
         18 . The method of  claim 10  wherein the vector having the AAV8 capsid is administered. 
     
     
         19 . The method of  claim 10  wherein the rAAV vector is endovascularly is administered. 
     
     
         20 . A method to inhibit or treat one or more symptoms associated with a deficiency in acid maltase in a human, consisting of: providing a human with a deficiency in acid maltase that is immunotolerized to acid maltase; and administering to the human an amount of a rAAV vector comprising a AAV8, AAV9 or AAVrh10 capsid encapsidating a rAAV genome having an open reading frame encoding acid maltase effective to inhibit or treat the one or more symptoms associated with the deficiency in acid maltase in the human. 
     
     
         21 . The method of  claim 20  wherein multiple doses of the rAAV vector are administered. 
     
     
         22 . The method of  claim 20  wherein the vector having the AAV9 capsid is administered. 
     
     
         23 . The method of  claim 20  wherein the vector having the AAVrh10 capsid is administered. 
     
     
         24 . The method of  claim 20  wherein the vector having the AAV8 capsid is administered. 
     
     
         25 . The method of  claim 20  wherein the rAAV vector is endovascularly administered. 
     
     
         26 . The method of  claim 20  wherein the amount administered reduces glycosaminoglycans (GAG).