METHOD FOR IMPROVING NEUROLOGICAL FUNCTION IN MPSI AND MPSII AND OTHER NEUROLOGICAL DISORDERS
A method to prevent, inhibit or treat one or more neurological symptoms associated with a central nervous system disorder, e.g. MPSI or MPSII by, for example, intrathecally, intracerebroventricularly or intravenously administering a rAAV encoding a gene product associated with the disease, e.g., administering to an adult mammal in which the gene product is absent, defective or present at a reduced level relative to a mammal without the disease.
1 . A method to prevent or inhibit neurocognitive deterioration, to enhance neurocognition, or recover neurologic function in a mammal manifesting or at risk of having Batten's disease, comprising: administering to the central nervous system of the mammal a composition comprising an amount of a recombinant adeno-associated virus (rAAV) vector comprising an open reading frame encoding a gene product of ceroid lipofuscinosis protein (CLN) 2 effective to prevent or inhibit neurocognitive deterioration, enhance neurocognition, or recover neurologic function.
2 . The method of claim 1 wherein the mammal is a human.
3 . The method of claim 1 , wherein the mammal is not an adult.
4 . The method of claim 2 , wherein the human is: i) about 6 to about 13 years old; ii) about 4 months to about 5 years old; or iii) less than 2.5 years old.
5 .- 6 . (canceled)
7 . The method of claim 2 , wherein the human has received an enzyme replacement therapy.
8 .- 13 . (canceled)
14 . The method of claim 1 , wherein the mammal is not treated with an immunosuppressant.
15 . The method of claim 1 , wherein the mammal is treated with an immunosuppressant.
16 . The method of claim 15 , wherein the rAAV and the immune suppressant are co-administered or the immune suppressant is administered after the rAAV.
17 . The method of claim 1 , wherein the mammal: i) is not immunotolerized prior to administration of rAAV; or ii) is immunotolerized prior to administration of rAAV.
18 . (canceled)
19 . The method of claim 1 , wherein the mammal is immunocompetent.
20 . The method of claim 1 , wherein the rAAV vector is a rAAV1, rAAV3, rAAV4, rAAV5, rAAVrh10, or rAAV9 vector.
21 .- 22 . (canceled)
23 . The method of claim 1 , wherein multiple doses are administered.
24 . (canceled)
25 . The method of claim 1 , wherein the rAAV is rAAV9 or rAAVrh10.
26 . The method of claim 1 , wherein the rAAV is intrathecally, intracerebrovascularly or intravenously administered.
27 . The method of claim 1 , wherein the rAAV is administered to the cisterna magna.
28 . The method of claim 15 , 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-β, IFN-γ, an opioid, or TNF-α (tumor necrosis factor-alpha) binding agent.
29 . The method of claim 1 , wherein the amount of rAAV administered is about 1.3×10 10 GC/g brain mass to about 6.5×10 10 GC/g brain mass.
30 . The method of claim 1 , wherein the amount of rAAV administered is about 1×10 3 GC per μL to about 1×10 15 GC per μL.
31 . The method of claim 1 , wherein the amount of rAAV administered is about 1×10 12 to about 5.6×10 13 GC (flat dose per mammal).
32 . The method of claim 1 , wherein the rAAV is intrathecally administered.