Intranasal delivery of 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 for treating or inhibiting one or more neurological signs or symptoms associated with a mucopolysaccharidosis in a mammal in need thereof, comprising:
intranasally administering an effective amount of an enzyme composition comprising alpha-L-iduronidase, iduronate-2-sulfatase, N-acetyl-alpha-D-glucosaminidase, betagalactosidase, or beta-glucuronidase.
2. The method of claim 1 wherein the administration inhibits neurological degeneration.
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 the mucopolysaccharidosis is related to a deficiency in alpha-L-iduronidase.
6. The method of claim 1 wherein the mucopolysaccharidosis is a mucopolysaccharide type I disorder, a mucopolysaccharidosis type II disorder, or a mucopolysaccharidosis type VII disorder.
7. The method of claim 1 wherein multiple doses are administered.
8. The method of claim 1 wherein the composition is administered weekly.
9. The method of claim 1 wherein the composition is administered daily.
10. The method of claim 1 wherein the pH of the composition is about 4 to about 9.
11. The method of claim 1 wherein the pH of the composition is about 5 to about 7.
12. The method of claim 1 wherein about 200 to about 400 μL of the composition is administered.
13. The method of claim 1 wherein the concentration of the enzyme in the composition is about 5 mg/mL to about 25 mg/mL.
14. The method of claim 1 wherein about 1 to about 7 mg of the enzyme is administered.
15. The method of claim 1 wherein the administration treats neurological degeneration.
16. The method of claim 1 wherein the composition is administered to the upper one third of the nasal cavity.
17. The method of claim 1 wherein the composition does not include a permeation enhancer.