Abstract: The present invention provides, among other things, methods and compositions for treating chronic lung disorders, in particular, bronchopulmonary dysplasia (BPD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to BPD an effective amount of an anti-Flt-1 antibody, or antigen binding fragment thereof, such that at least one symptom or feature of BPD is reduced in intensity, severity, or frequency, or has delayed onset.

Abstract: The present invention provides compounds and compositions thereof which are useful as inhibitors of plasma kallikrein and which exhibit desirable characteristics for the same.

Abstract: The present invention provides, among other things, methods and compositions for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of a recombinant PLGF protein such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset. The present invention also provides exemplary recombinant PLGF proteins including monomeric, dimeric and single-chain PLGF proteins.

Abstract: A targeted therapeutic including a lysosomal enzyme and a lysosomal targeting moiety that is a peptide containing at least one N-linked glycosylation site. Methods of producing the targeted therapeutic may include nucleotide acids encoding the same and host cells co-expressing GNPT. Pharmaceutical compositions comprising the targeted therapeutic and methods of using the same to treat a lysosomal storage disease.

Abstract: The present invention provides, among other things, methods and compositions for treating muscular dystrophy, in particular, Duchenne muscular dystrophy (DMD). In some embodiments, a method according to the present invention includes administering to an individual who is suffering from or susceptible to DMD an effective amount of a recombinant follistatin protein such that at least one symptom or feature of DMD is reduced in intensity, severity, or frequency, or has delayed onset.

Abstract: The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease), In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.

Abstract: 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.

Abstract: The present invention provides, among other things, effective treatment for Sanfilippo Syndrome Type A (MPS IIIA) based on intrathecal delivery of recombinant heparan N-sulfatase (HNS) enzyme. The present invention also includes methods of treating Sanfilippo Syndrome Type A (MPS IIIA) Syndrome by intrathecal administration of a recombinant HNS enzyme at a therapeutically effective dose and an administration interval for a period sufficient to decrease glycosaminoglycan (GAG) heparan sulfate level in the cerebrospinal fluid (CSF) relative to baseline (e.g., prior to treatment) as well as to improve, stabilize, or reduce decline of cognitive function, disability, behavior, quality of life and/or auditory brainstem response relative to baseline (e.g., prior to treatment).

Abstract: The invention provides compositions and methods for effective lysosomal targeting mediated by SORT1. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Sanfilippo syndrome type B.

Abstract: Detecting glycosaminoglycans (GAGs) and/or determining the level of one or more glycosaminoglycans can be useful, e.g., in identifying or monitoring various medical conditions, the status of patients having various medical conditions, and/or the response to treatment of individuals having various medical conditions. The present invention provides methods for detecting glycosaminoglycans and/or determining the level of glycosaminoglycans through the use of, e.g., mass spectrometry.

Abstract: 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.

Abstract: 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.

Abstract: The present invention provides, among other things, oligonucleotide modulators of human 5?-HT2C receptor (HTR2C) and improved methods and composition for treating HTR2C-related diseases, disorders or conditions based on such modulators. In particular, oligonucleotides modulators according to the invention target specific regions in the Exon V/Intron V junction of the human HTR2C pre-mRNA and drive expression of HTR2C Vb splice isoform, leading to increased generation of non-edited strong HTR2C receptor and enhanced serotonin receptor activity.

Abstract: The invention provides methods of treating ?-galactosidase A deficiency. Dosage forms, methods of administration, and methods of analyzing human ?-galactosidase A are also included.

Abstract: The present invention provides, among other things, improved methods for purifying I2S protein produced recombinantly for enzyme replacement therapy. The present invention is, in part, based on the surprising discovery that recombinant I2S protein can be purified from unprocessed biological materials, such as, I2S-containing cell culture medium, using a process involving as few as four chromatography columns.

Abstract: Methods of producing arylsulfatase A are described herein. The methods can include one or more steps of chromatography. Exemplary chromatographic steps include ion exchange chromatography, mixed mode chromatography, and hydrophobic interaction chromatography. Compositions containing and methods using arylsulfatase A produced by the methods described herein are also disclosed.

Abstract: The invention provides methods of treating ?-galactosidase A deficiency. Dosage forms, methods of administration, and methods of analyzing human ?-galactosidase A are also included.

Abstract: The invention features a method of producing a high mannose glucocerebrosidase (hmGCB) which includes: providing a cell which is capable of expressing glucocerebrosidase (GCB), and allowing production of GCB having a precursor oligosaccharide under conditions which prevent the removal of at least one mannose residue distal to the pentasaccharide core of the precursor oligosaccharide of GCB, to thereby produce an hmGCB preparation. Preferably, the condition which prevents the removal of at least one mannose residue distal to the pentasaccharide core is inhibition of a class 1 processing mannosidase and/or a class 2 processing mannosidase. The invention also features an hmGCB preparation and methods of using an hmGCB preparation.

Abstract: The present invention provides, among other things, methods for the characterization of recombinant Heparan N-Sulfatase (HNS) during manufacture. The present invention uses capillary zone electrophoresis to determine the charge profile, isoform distribution, and/or glycan profile of recombinant HNS; and represents a quality feature for the batch consistency, storage stability, biological half-life, pharmacokinetic, pharmacodynamic and biological activity of the enzyme. In particular, such characterization methods may be beneficial to optimize conditions and ensure consistency for the manufacture of HNS for the treatment of a patient diagnosed with Sanfilippo syndrome using enzyme replacement therapy.

Abstract: In some embodiments, the present invention provides method of identifying compounds that bind to phosphoinositol 4-phosphate adaptor protein-2 (FAPP2), including the steps of computationally identifying a compound that binds to FAPP2 using the atomic coordinates of at least the amino acids which make up the substrate binding pocket of FAPP2. Also provided are methods of designing, selecting and/or optimizing a compound that binds to FAPP2.