Provided herein are methods and compositions for treating a subject suffering from a deficiency in iduronate 2-sulfatase in the CNS. The methods include systemic administration of a bifunctional fusion antibody comprising an antibody that crosses the blood brain barrier (BBB) and an iduronate 2-sulfatase.

The present invention provides new Adeno-associated virus-derived vectors and pharmaceutical compositions containing the same for the treatment of lysosomal storage disorders and specially, for the treatment of mucopolysaccharidoses Type II.

A transgenic mouse expressing inactivated human iduronate-2-sulphatase (IDS) and a method for improving agents for treating Hunter syndrome using the transgenic mouse are provided. The transgenic mouse expressing the inactivated human IDS, which has immune tolerance to IDS, does not cause an immune response to IDS which is an active component of the agents for treating Hunter syndrome, and thus the transgenic mouse may be effectively used to identify immunogenic factors other than the immunogenicity of the protein components of the agents.

Disclosed are a novel anti-human transferrin receptor antibody comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 4, 5, 6 and 7 that can pass through the blood-brain barrier, a fusion protein comprising a protein necessary to be brought into function in the central nervous system and the antibody, and method of their production. The fusion protein comprises amino acid sequences of an anti-human transferrin receptor antibody that recognizes an amino acid sequence selected from the group consisting of SEQ ID NOs:1, 2, and 3, and of other protein that is bound thereto on the C-terminal side.

Provided is a modified iduronate-2-sulfatase (IDS) gene constructed by inserting the nucleotide of SEQ ID NO: 2 into a wild-type IDS gene. In addition to being negatively charged, the improved IDS enzyme encoded by the modified gene exhibits a sufficient retention time in blood to target the bone, so that it is more effective for treating Hunter syndrome.

A composition comprising recombinant iduronate-2-sulfatase (IDS) and a method for producing a purified recombinant IDS are provided. The glycosylation pattern and formylglycine content of the IDS composition are different from those of ELAPRASE and have superior pharmaceutical efficacy and are safer than the conventional agent and thus can be effectively used for the therapy of Hunter Syndrome.

This invention relates to viral vectors for delivery of iduronate-2-sulfatase (IDS) to a subject. In some aspects the IDS sequence is optimized for expression in human cells. The invention further relates to methods of using the vector to increase secretion of IDS from a cell and for treatment and prevention of mucopolysaccharidosis II.

Among other things, the present invention provides methods and compositions of treating Sanfilippo syndrome type B (Sanfilippo B) by, e.g., intrathecal (IT) administration of a Naglu protein. A suitable Naglu protein can be a recombinant, gene-activated or natural protein. In some embodiments, a suitable Naglu protein is a recombinant Naglu protein. In some embodiments, a recombinant Naglu protein is a fusion protein containing a Naglu domain and a lysosomal targeting moiety. In some embodiments, the lysosomal targeting domain is an IGF-II moiety.

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

The present invention, provides a method of treating cognitive impairment of Hunter syndrome. Among other things, the present invention provides a method comprising a step of administering intrathecally to a subject in need of treatment a recombinant iduronate-2-sulfatase (I2S) enzyme at a therapeutically effective dose and an administration interval for a treatment period sufficient to improve, stabilize or reduce declining of one or more cognitive, adaptive, motor, and/or executive functions relative to a control