Abstract: The present disclosure provides, among other things, a method of treating Fabry disease in a subject, the method comprising administering to a subject in need thereof a recombinant adeno-associated viral vector (rAAV) packaged in AAV capsid having broad tissue tropism, the vector comprising: (a) a 5? inverted terminal repeat; (b) a ubiquitous promoter; (c) a nucleotide sequence encoding wild-type ?-GAL enzyme or a variant thereof; (d) optionally a woodchuck hepatitis virus posttranscriptional regulatory element (WPRE); (e) a poly A; and (d) a 3?ITR.

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 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: 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 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.