Intranasal delivery of AAV encoding therapeutic enzymes to the central nervous system for the treatment of lysosomal storage diseases
The invention provides a method to prevent, inhibit or treat one or more neurological symptoms associated with a lysosomal storage disease in a mammal in need thereof, which includes intranasally administering to the mammal a composition comprising an effective amount of a lysosomal storage enzyme or a recombinant adeno-associated virus vector comprising an open reading frame encoding a lysosomal storage enzyme. Also provided are compositions and devices useful in the methods.
1. A method to prevent, inhibit or treat one or more neurological signs or symptoms associated with a deficiency in alpha-L-iduronidase, iduronate-2-sulfatase, N-acetyl-alpha-D-glucosaminidase, beta-galactosidase, or beta-glucuronidase in a mammal in, comprising: intranasally administering to the mammal a composition comprising an amount of a recombinant adeno-associated virus vector comprising an open reading frame encoding a lysosomal storage enzyme comprising alpha-L-iduronidase, iduronate-2-sulfatase, N-acetyl-alpha-D-glucosaminidase, beta-galactosidase, or beta-glucuronidase, effective to prevent, inhibit or treat the one or more neurological signs or symptoms associated with the deficiency.
2. The method of claim 1 wherein the administration prevents or inhibits the one or more signs or symptoms.
3. The method of claim 1 wherein the enzyme is alpha-L-iduronidase.
4. The method of claim 1 wherein the mammal is a human.
5. The method of claim 1 wherein multiple doses are administered.
6. The method of claim 1 wherein the composition is administered weekly.
7. The method of claim 1 wherein the composition is administered daily.
8. The method of claim 1 wherein the pH of the composition is about 4 to about 9.
9. The method of claim 1 wherein the pH of the composition is about 5 to about 7.
10. The method of claim 1 wherein about 200 to about 400 μL of the composition is administered.
11. The method of claim 1 wherein the administration treats the one or more signs or symptoms.
12. The method of claim 1 wherein the composition is administered to the upper one third of the nasal cavity.
13. The method of claim 1 wherein the mammal has Hurler syndrome.
14. The method of claim 1 wherein the mammal has Hurler-Scheie syndrome.
15. The method of claim 1 wherein the mammal has Scheie syndrome.
16. The method of claim 1 wherein about 50 μL to about 500 μL of the composition is administered.