Lysosomal storage diseases can be successfully treated using intraventricular delivery of the enzyme which is etiologically deficient in the disease. The administration can be performed slowly to achieve maximum effect. Surprisingly, effects are seen on both sides of the blood-brain barrier, making this an ideal delivery means for lysosomal storage diseases which affect both brain and visceral organs.

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.

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 relates to a compound comprising an antibody or a fragment thereof operable to transmigrate across the blood-brain barrier (BBB), and a polypeptide related to the treatment of lysosomal storage disease (LSD), for the treatment of α-synucleinopathies, or both. The present invention also relates to pharmaceutical compositions and methods for 5 treating LSDs, treating, α-synucleinopathies, or both.

Embodiments disclosed herein provide compositions for conjugates, including fusion proteins, and methods of using them to treat a variety of conditions. In some embodiments, the conjugates and/or fusion proteins incorporate a 60-amino acid human homeodomain (e.g., peptides derived from human HOX genes), to translocate functional and regulatory peptides and proteins or other biologically active molecules such as nucleic acids, which are not naturally associated with the human homeodomain, across cell and nuclear membranes to intended sites of action without provoking an unwanted immune response that may reduce exposure to the conjugate and/or result in a clinical adverse event. In further embodiments, disclosed conjugates and fusion proteins can pass through the blood-brain barrier to allow entry into the CNS. In various embodiments, the disclosed compositions are suitable for delivery into a cell (i) the expression product of a gene of interest and/or (ii) novel peptides or polynucleotides to regulate gene function.

[Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market.

[Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.

Provided herein are fusion proteins that comprise an enzyme replacement therapy enzyme and an Fc region, as well as methods of using such proteins to treat a lysosomal storage disorder. Methods for transporting agents across the blood-brain barrier are also provided herein.

Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.

Compositions and methods for delivering enzymes in enzyme hydrogel formulations are disclosed. More particularly, the present disclosure relates to injectable enzyme hydrogel formulations and delivery of injectable enzyme hydrogel formulations. Also disclosed are methods for GALNS enzyme replacement therapy and lysosomal enzyme replacement therapy.

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.