Methods for use of viral vector constructs for the treatment of fabry disease

A method of treating Fabry disease or ameliorating one or more symptoms associated with Fabry disease in a human subject in need thereof, the method comprising administering to the subject an adeno-associated virus (AAV) expression vector comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an α galactosidase A (α-Gal A) transgene encoding the at least one α-Gal A protein, wherein the α-GalA transgene comprises the nucleotide sequence as set forth in SEQ ID NO:

• 5, wherein the AAV expression vector is administered at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg.

A method of reducing the amount of glycosphingolipids in a human subject in need thereof, the method comprising administering to the subject an adeno-associated virus (AAV) expression vector comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an apolipoprotein E (APOE) enhancer operably linked to an alpha 1-antitrypsin (hAAT) promoter, a human hemoglobin beta (HBB)-IGG intron, a sequence encoding a signal peptide, an α galactosidase A (α-Gal A) transgene encoding the at least one α-Gal A protein, and a bovine growth hormone poly A signal sequence, wherein the AAV expression vector is administered at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg, wherein the reduced amount of glycosphingolipids is relative to the amount of glycosphingolipids in the subject prior to the administration.

A method of reducing the amount of glycosphingolipids in a human subject in need thereof, the method comprising administering to the subject an adeno-associated virus (AAV) expression vector comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an α galactosidase A (α-Gal A) transgene encoding the at least one α-Gal A protein, wherein the α-GalA transgene comprises the nucleotide sequence as set forth in SEQ ID NO:

• 5, wherein the AAV expression vector is administered at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg, wherein the reduced amount of glycosphingolipids is relative to the amount of glycosphingolipids in the subject prior to the administration.

A method of increasing an α galactosidase A (α-Gal A) protein activity in a human subject in need thereof, the method comprising administering to the subject an adeno-associated virus (AAV) expression vector comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an apolipoprotein E (APOE) enhancer operably linked to an alpha 1-antitrypsin (hAAT) promoter, a human hemoglobin beta (HBB)-IGG intron, a sequence encoding a signal peptide, an α-Gal A transgene encoding the at least one α-Gal A protein, and a bovine growth hormone poly A signal sequence, wherein the AAV expression vector is administered at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg, wherein the increased α-Gal A protein activity is relative to the α-Gal A protein activity in the subject prior to the administration.

A method of increasing an α galactosidase A (α-Gal A) protein activity in a human subject in need thereof, the method comprising administering to the subject an adeno-associated virus (AAV) expression vector comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an α-Gal A transgene encoding the at least one α-Gal A protein, wherein the α-GalA transgene comprises the nucleotide sequence as set forth in SEQ ID NO:

• 5, wherein the AAV expression vector is administered at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg, wherein the increased α-Gal A protein activity is relative to the α-Gal A protein activity in the subject prior to the administration.

The method of any one of claims 1 to 50, wherein the expression of the at least one α-Gal A protein is sustained for at least 3 months, at least 4 months, at least 5 months, at least 6 months, at least 7 months, at least 8 months, at least 9 months, at least 10 months, at least 11 months, at least 12 months, at least 13 months, at least 14 months, at least 15 months, at least 16 months, at least 17 months, at least 18 months, at least 19 months, at least 20 months, at least 21 months, at least 22 months, at least 23 months, or at least 24 months.