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: Described herein is an implantable access port device with a catheter compartment which permits lengthening or shortening the catheter in response to changes in tension of the distal catheter. Implantable access port devices are used extensively in the medical field to facilitate the performance of recurrent therapeutic tasks such as repeated drug delivery, drainage, blood sampling, transfusions, or total parental nutrition. In current access port systems, the catheter is rigidly attached to the access port via a connection ring. As such, the system does not provide any flexibility or ability for catheter length adjustments, which can lead to long-term complications such as dislodgement of catheters, migration of catheters, port separation with extravasation, suture disruption, and mechanical failure of the access port system. These catheter-related complications carry serious risks for the patients.

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: Described herein is an implantable access port device with a catheter compartment which permits lengthening or shortening the catheter in response to changes in tension of the distal catheter. Implantable access port devices are used extensively in the medical field to facilitate the performance of recurrent therapeutic tasks such as repeated drug delivery, drainage, blood sampling, transfusions, or total parental nutrition. In current access port systems, the catheter is rigidly attached to the access port via a connection ring. As such, the system does not provide any flexibility or ability for catheter length adjustments, which can lead to long-term complications such as dislodgement of catheters, migration of catheters, port separation with extravasation, suture disruption, and mechanical failure of the access port system. These catheter-related complications carry serious risks for the patients.

Abstract: The present invention provides, among other things, a method of ocular delivery of messenger RNA (mRNA), comprising administering into an eye of a subject in need of delivery a composition comprising an mRNA encoding a protein, such that the administration of the composition results in expression of the protein encoded by the mRNA in the eye.

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 disclosure provides a method for treating symptomatic orthostatic hypotension using a potent selective antagonist of N-methyl-D-aspartate receptor subunit 2B (NMDA-GluN2B or NR2B).

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

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: Described herein is an implantable access port device with a catheter compartment which permits lengthening or shortening the catheter in response to changes in tension of the distal catheter. Implantable access port devices are used extensively in the medical field to facilitate the performance of recurrent therapeutic tasks such as repeated drug delivery, drainage, blood sampling, transfusions, or total parental nutrition. In current access port systems, the catheter is rigidly attached to the access port via a connection ring. As such, the system does not provide any flexibility or ability for catheter length adjustments, which can lead to long-term complications such as dislodgement of catheters, migration of catheters, port separation with extravasation, suture disruption, and mechanical failure of the access port system. These catheter-related complications carry serious risks for the patients.

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, 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 5% of the ASA protein exists in aggregated form.

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 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, 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 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.