Use of p97 as an enzyme delivery system for the delivery of therapeutic lysosomal enzymes
The present invention provides for compositions and methods for treating, ameliorating or preventing a lysosomal storage disease by administering to a patient suffering from a lysosomal storage disease a P97 conjugated with an enzyme which is capable of transportation into the lysosomes of cells on either sides of the blood brain barrier.
1. A method for treating a lysosomal storage disease in a human in need thereof, comprising administering a p97 conjugate to the human, wherein the p97 conjugate comprises a p97 protein or an active fragment or variant thereof covalently linked to a lysosomal storage disease enzyme.
2. The method of claim 1 , wherein said p97 protein is a soluble p97 protein.
3. The method of claim 1 , wherein said p97 protein is a human p97 protein.
4. The method of claim 1 , wherein said p97 protein is a human, soluble p97 protein.
5. The method of claim 1 , wherein said p97 protein is a biologically active fragment of a human p97 protein.
6. The method of claim 1 , wherein the p97 protein is covalently linked to said agent of interest with a linker.
7. The method of claim 1 , where the lysosomal storage disease enzyme is selected from the group consisting of α-L-iduronidase, iduronate-2-sulfatase, heparan-N-sulfatase, α-N-acetylglucosaminidase, arylsulfatase A, galactosylceramidase, acid-α-glucosidase, thioesterase, hexosaminidase A, acid sphingomyelinase, and α-galactosidase.
8. The method of claim 1 , where the lysosomal storage disease enzyme is iduronate-2-sulfatase.
9. The method of claim 1 , wherein the conjugate is a fusion protein.
10. The method of claim 1 , wherein the lysosomal storage disease enzyme is α-L-iduronidase.