METHODS TO TREAT CEROID LIPOFUSCINOSIS USING A RECOMBINANT ADENO-ASSOCIATED VIRUS
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.
1 . A method to inhibit or treat one or more symptoms of ceroid lipofuscinosis 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 a lysosomal enzyme effective to inhibit or treat the one or more symptoms of ceroid lipofuscinosis.
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 said lysosomal enzyme.
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 ceroid lipofuscinosis 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 a lysosomal enzyme effective to inhibit or treat the one or more symptoms of ceroid lipofuscinosis.
10 . The method of claim 9 wherein the immune suppressant comprises cyclophosphamide.
11 . The method of claim 9 wherein the immune suppressant comprises a glucocorticoid, cytostatic agents including an alkylating agent, an anti-metabolite, a cytotoxic antibiotic, an antibody, or an agent active on immunophilin.
12 . The method of claim 9 wherein the immune suppressant comprises a nitrogen mustard, nitrosourea, platinum compound, methotrexate, azathioprine, mercaptopurine, fluorouracil, dactinomycin, an anthracyclin e, 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.
13 . 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.
14 . The method of claim 9 wherein the rAAV vector is a rAAV-9 vector,
15 . The method of claim 9 wherein multiple doses of the composition comprising the rAAV9 or rAAVrh10 vector are administered.
16 . The method of claim 9 wherein the rAAV vector is rAAVrh10 vector.
17 . The method of claim 9 wherein the immune suppressant is administered before the rAAV9 or rAAVrh10 vector.
18 . The method of claim 9 wherein the immune suppressant is systemically administered.
19 . The method of claim 9 wherein the mammal is a human.
20 . The method of claim 9 wherein the amount administered reduces glycosaminoglycans (GAG).