Methods and compositions for increasing iduronate 2-sulfatase activity in the CNS

A method for increasing iduronate-2-sulfatase (IDS) activity in a central nervous system of a subject with Hunter's syndrome, comprising systemically administering to the subject with Hunter's syndrome a therapeutically effective dose of a fusion antibody comprising:

• (a) an immunoglobulin that crosses a blood brain barrier (BBB), wherein the immunoglobulin comprises an immunoglobulin heavy chain;
• and
• (b) an iduronate-2-sulfatase, wherein the amino acid sequence of the iduronate-2-sulfatase is covalently linked to the amino terminus of the amino acid sequence of the immunoglobulin heavy chain, thereby forming a fusion protein;
• wherein the fusion antibody crosses the blood brain barrier (BBB) and catalyzes hydrolysis of 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate or heparin, wherein the iduronate-2-sulfatase retains at least 20% of its activity compared to its activity as a separate entity after crossing a BBB of the subject with Hunter's syndrome and entering a lysosomal compartment of a cell in a central nervous system of the subject with Hunter's syndrome, and wherein the iduronate-2-sulfatase specific activity of the fusion antibody is at least 10,000 units/mg.