Abstract: Provided herein are methods of treating or ameliorating hypercholemia or a cholestatic liver disease by administering to an individual in need thereof a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising administering to an individual in need thereof a therapeutically effective amount of ASBTI or a pharmaceutically acceptable salt thereof.

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: Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

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: Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

Abstract: Provided herein are methods of treating or ameliorating a pediatric cholestatic liver disease by non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof. Also provided are methods for treating or ameliorating a pediatric liver disease, decreasing the levels of serum bile acids or hepatic bile acids, treating or ameliorating pruritis, reducing liver enzymes, or reducing bilirubin comprising non-systemically administering to an individual in need thereof a therapeutically effective amount of a pediatric formulation comprising an ASBTI or a pharmaceutically acceptable salt thereof.

Abstract: The present disclosure is directed to a vial adapter for interconnecting a vial and a fluid delivery device, and, more particularly, to a vial adapter having a modular design consisting of separately constructed components cooperatively arranged and coupled to one another. The modular construction allows for rapid manufacturing reconfigurations of one or more components with minimal costs to create new vial adapter configurations that meet specific needs.

Abstract: Plunger rod stops attach to existing syringes to limit the range of motion of the plunger, thereby to precisely control the amount of liquid that can be expelled from the syringe when the plunger rod stop is in place. In some embodiments, plunger rod stop devices generally include a body configured to attach to the plunger, and a stand-off extending from the body, configured to contact the finger flange when the plunger is depressed. In other embodiments, the plunger rod stop attaches to the finger flange or other fixed component of the syringe and the stand-off is configured to contact the plunger or plunger rod. Methods of the invention involve using the devices to interfere with the range of motion of the plunger, then reconfiguring or removing the device to allow the plunger to be moved a predetermined length, which corresponds to a precise dosage amount.

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 disclosure is directed to a vial adapter for interconnecting a vial and a fluid delivery device, and, more particularly, to a vial adapter having a modular design consisting of separately constructed components cooperatively arranged and coupled to one another. The modular construction allows for rapid manufacturing reconfigurations of one or more components with minimal costs to create new vial adapter configurations that meet specific needs.

Abstract: Plunger rod stops attach to existing syringes to limit the range of motion of the plunger, thereby to precisely control the amount of liquid that can be expelled from the syringe when the plunger rod stop is in place. In some embodiments, plunger rod stop devices generally include a body configured to attach to the plunger, and a stand-off extending from the body, configured to contact the finger flange when the plunger is depressed. In other embodiments, the plunger rod stop attaches to the finger flange or other fixed component of the syringe and the stand-off is configured to contact the plunger or plunger rod. Methods of the invention involve using the devices to interfere with the range of motion of the plunger, then reconfiguring or removing the device to allow the plunger to be moved a predetermined length, which corresponds to a precise dosage amount.

Abstract: The present invention is directed, in part, to the treatment of a subject having a neurodegenerative disorder, such as Parkinson's disease (PD), by providing glucocerebrosidase enzyme. The enzyme may be provided, e.g., through gene therapy or by administration of a glucocerebrosidase protein. Accordingly, the present invention encompasses glucocerebrosidase nucleic acids or proteins for use in the treatment of PD or other neurodegenerative disorders.

Abstract: A drug monitoring tool comprises a data receiver and an interactive user interface. The data receiver is configured to receive a pharmacokinetic (PK) profile of a patient. The interactive user interface is configured to display, to the patient, a time-varying therapeutic plasma protein level of the patient and delineate a plurality of zones within the interactive user interface associated with the time-varying therapeutic plasma protein level. The plurality of zones includes a safe zone indicating to the patient that the time-varying therapeutic plasma protein level is within a first concentration range considered safe for physical activity and a danger zone indicating to the patient that the time-varying therapeutic plasma protein level is within a second concentration range and physical activity should be limited.

Abstract: The invention relates to an affinity resin functionalized with small molecule inhibitors of glycoside-cleaving enzymes, e.g., ?-galactosidase A (?-Gal A), glucocerebrosidase (GCB), ?-galactosidase, and acid alpha-glucosidase (GAA), and a method for purifying glycoside-cleaving enzymes produced in a cell line using the small molecule inhibitor-functionalized affinity resin.

Abstract: Embodiments of the present disclosure relate to a drug monitoring tool. The drug monitoring tool comprises a data receiver and an interactive user interface. The data receiver is configured to receive a pharmacokinetic (PK) profile of a patient. The interactive user interface is configured to display, to the patient, a time-varying therapeutic plasma protein level of the patient. The time-varying therapeutic plasma protein level is based on an administered dose of a clotting factor VIII and the PK profile of the patient.

Abstract: The invention provides a composition of glucocerebrosidase, such as velaglucerase alfa, and isofagomine, in a molar ratio of at least about 1:2.5. Also provided is a use of the composition for treatment of a disorder related to a dysfunction in a GCase pathway. The disorder could be a lysosomal storage disease, such as Gaucher disease, Fabry disease, Pompe disease, a mucopolysaccharidoses, or multiple system atrophy. The disorder could also be a neurodegenerative disorder, such as Parkinson disease, Alzheimer's disease, or Lewy body dementia. The composition can have 0.5 to 5.0 mg/kg of glucocerebrosidase and isofagomine in at least about a 3-fold molar excess to the glucocerebrosidase. The composition can be administered intravenously or subcutaneously.

Abstract: The present invention provides, among other things, anti-Flt-1 antibodies and methods 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 an anti-Flt-1 antibody or antigen-binding protein thereof 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 other things, methods and compositions for determining enzyme kinetic parameters (e.g., Vmax, Km, and specific activity, etc.) indicative of clinically relevant properties of glucocerebrosidase using a physiologically relevant substrate, in particular, a substrate that is representative of substrates that typically accumulate in patients suffering from Gaucher disease such as glucosylceramide. Thus, the present invention is particularly useful to measure a kinetic parameter relating to the activity of glucocerebrosidase in a drug substance, drug product, and stability sample for enzyme replacement therapy.