Abstract: The present invention provides compositions and methods for effective treatment of a lysosomal acid lipase deficiency (LALD) disease, in particular, Wolman's disease and Cholesteryl Ester Storage Disease (CESD). Among other things, the present invention provides a method of treating developmental impairment or malnutrition in an individual suffering from a lysosomal acid lipase deficiency (LALD) disease, comprising administering to the individual a therapeutic effective amount of a lysosomal acid lipase.

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: Formulations for controlled, sustained release of biologically active agents for the treatment of ocular disorders have been developed. These formulations are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. The microparticles are characterized by low burst levels and efficient drug loading and sustained release.

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

Abstract: The present invention discloses polymeric materials that incorporate a modified quinone moiety, either to cross-link the polymer or as a monomeric unit of the polymer. These polymeric materials can be efficiently degraded through electrochemical reduction of the quinone leading to rapid hydrolysis of the pendant chemical groups and degradation of the polymer. Quinone-containing compositions and methods of producing electrochemically degradable polymers are disclosed. The methods and compositions of the present invention can be used in a wide variety of applications, including, but not limited to, drug delivery, tissue regeneration, biomedical implants, and electronic systems.

Abstract: The present invention provides compositions and methods for effective treatment of a lysosomal acid lipase deficiency (LALD) disease, in particular, Wolman's disease and Cholesteryl Ester Storage Disease (CESD). Among other things, the present invention provides a method of treating developmental impairment or malnutrition in an individual suffering from a lysosomal acid lipase deficiency (LALD) disease, comprising administering to the individual a therapeutic effective amount of a lysosomal acid lipase.

Abstract: 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.

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 B-Galactocerebrosidase protein, salt, and a polysorbate surfactant for the treatment of GLD Disease.

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

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 a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

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 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: 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.

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

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 B-Galactocerebrosidase protein, salt, and a polysorbate surfactant for the treatment of GLD Disease.

Abstract: The invention provides methods and compositions for detecting and/or quantifying modified nucleic acid oligonucleotides. These methods and compositions are useful for detecting and quantifying diagnostic and/or therapeutic synthetic modified oligonucleotides, such as aptamers, RNAi, siRNA, antisense oligonucleotides or ribozymes in a biological sample.

Abstract: The present invention discloses polymeric materials that incorporate a modified quinone moiety, either to cross-link the polymer or as a monomeric unit of the polymer These polymeric materials can be efficiently degraded through electrochemical reduction of the quinone leading to rapid hydrolysis of the pendant chemical groups and degradation of the polymer. Quinone-containing compositions and methods of producing electrochemically degradable polymers are disclosed. The methods and compositions of the present invention can be used in a wide variety of applications, including, but not limited to, drug delivery, tissue regeneration, biomedical implants, and electronic systems.

Abstract: The invention relates to immunomodulatory compositions and related methods. The immunomodulatory compositions of a formula disclosed herein are useful for the prevention of sepsis and the treatment and prevention of diseases associated with inflammation and/or NOS.

Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.

Abstract: Formulations for controlled, sustained release of biologically active agents for the treatment of ocular disorders have been developed. These formulations are based on solid microparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. The microparticles are characterized by low burst levels and efficient drug loading and sustained release.