Provided herein is a method for reducing the progression of abnormal muscle pathology and/or reversing abnormal muscle pathology in a patient, wherein the patient has been diagnosed with Pompe disease or is suspected of having Pompe disease. The method comprising administering to the patient a recombinant AAV (rAAV) having an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises: (a) a 5′ inverted terminal repeat (ITR); (b) a promoter; (c) a nucleotide sequence encoding a chimeric fusion protein comprising a signal peptide and a vIGF2 peptide fused to a human acid-a-glucosidase (hGAA), (d) a poly A; and (e) a 3′ ITR. Also provided are pharmaceutical composition comprising an rAAV described herein for use in treating a patient having or suspected of having Pompe disease.

Provided herein are fusion proteins comprising a first domain that specifically binds to the extracellular domain of a growth factor receptor, and a second domain that specifically binds to a cartilage matrix component, and pharmaceutical composition comprising these fusion proteins. Methods of treating musculoskeletal diseases using the fusion proteins and pharmaceutical composition disclosed herein are also provided.

Provided herein are fusion proteins comprising a first domain that specifically binds to the extracellular domain of a growth factor receptor, and a second domain that specifically binds to a cartilage matrix component, and pharmaceutical composition comprising these fusion proteins. Methods of treating musculoskeletal diseases using the fusion proteins and pharmaceutical composition disclosed herein are also provided.

The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

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 iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

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 iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

The present invention provides further improved compositions and methods for efficient lysosomal targeting based on the GILT technology. Among other things, the present invention provides methods and compositions for targeting lysosomal enzymes to lysosomes using furin-resistant lysosomal targeting peptides. The present invention also provides methods and compositions for targeting lysosomal enzymes to lysosomes using a lysosomal targeting peptide that has reduced or diminished binding affinity for the insulin receptor.

The present invention provides further improved compositions and methods for efficient lysosomal targeting based on the GILT technology. Among other things, the present invention provides methods and compositions for targeting lysosomal enzymes to lysosomes using furin-resistant lysosomal targeting peptides. The present invention also provides methods and compositions for targeting lysosomal enzymes to lysosomes using a lysosomal targeting peptide that has reduced or diminished binding affinity for the insulin receptor.

Tools for characterizing uptake of therapeutic compounds by target tissue are disclosed along with methods for determining dosing regimen from the uptake parameters. Uptake parameters considered include partition coefficient, diffusivity, and equilibrium uptake ratio. Systems for determining partition coefficient and diffusivity in rapid uptake combinations of compounds and tissue are also reported.