ganglio-n-triaosylceramide and Sandhoff-Disease

ganglio-n-triaosylceramide has been researched along with Sandhoff-Disease* in 2 studies

Other Studies

2 other study(ies) available for ganglio-n-triaosylceramide and Sandhoff-Disease

Article	Year
Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents pathology in Sandhoff disease mice. Human molecular genetics, 2018, 03-15, Volume: 27, Issue:6 Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of β-hexosaminidase activity which is fatal because no effective treatment is available. A mouse model of Hexb deficiency reproduces the key pathognomonic features of SD patients with severe ubiquitous lysosomal dysfunction, GM2 accumulation, neuroinflammation and neurodegeneration, culminating in death at 4 months. Here, we show that a single intravenous neonatal administration of a self-complementary adeno-associated virus 9 vector (scAAV9) expressing the Hexb cDNA in SD mice is safe and sufficient to prevent disease development. Importantly, we demonstrate for the first time that this treatment results in a normal lifespan (over 700 days) and normalizes motor function assessed by a battery of behavioral tests, with scAAV9-treated SD mice being indistinguishable from wild-type littermates. Biochemical analyses in multiple tissues showed a significant increase in hexosaminidase A activity, which reached 10-15% of normal levels. AAV9 treatment was sufficient to prevent GM2 and GA2 storage almost completely in the cerebrum (less so in the cerebellum), as well as thalamic reactive gliosis and thalamocortical neuron loss in treated Hexb-/- mice. In summary, this study demonstrated a widespread protective effect throughout the entire CNS after a single intravenous administration of the scAAV9-Hexb vector to neonatal SD mice. Topics: Administration, Intravenous; Animals; Animals, Newborn; Brain; Disease Models, Animal; Female; G(M2) Ganglioside; Gangliosides; Hexosaminidase B; Male; Mice; Mice, Inbred C57BL; Sandhoff Disease	2018
Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay. Neurochemical research, 1999, Volume: 24, Issue:2 The interaction between glycosphingolipids and recombinant human GM2-activator was studied in a microwell binding assay. A-series gangliosides like GM3, GM2 and GM1 were strongly bound by the recombinant human GM2 activator. A weak binding was observed to GD1b and sulfatide, while neutral glycolipids were not bound. Optimal binding occurred at pH 4.2 and was inhibited by increasing concentrations of citrate buffer and NaCl. In contrast with these in vitro results the recombinant human GM2-activator is able to restore the degradation of GA2 in fibroblasts from patients with the AB variant of GM2 gangliosidosis in vivo. Topics: Biotin; Cells, Cultured; Citrates; Fibroblasts; G(M2) Activator Protein; Gangliosides; Gangliosidoses; Glycosphingolipids; Humans; Hydrogen-Ion Concentration; Infant; Protein Binding; Proteins; Recombinant Proteins; Sandhoff Disease; Sodium Chloride; Tay-Sachs Disease	1999

Article

Year

Intravenous administration of scAAV9-Hexb normalizes lifespan and prevents pathology in Sandhoff disease mice.

Human molecular genetics, 2018, 03-15, Volume: 27, Issue:6

Sandhoff disease (SD) is a rare inherited disorder caused by a deficiency of β-hexosaminidase activity which is fatal because no effective treatment is available. A mouse model of Hexb deficiency reproduces the key pathognomonic features of SD patients with severe ubiquitous lysosomal dysfunction, GM2 accumulation, neuroinflammation and neurodegeneration, culminating in death at 4 months. Here, we show that a single intravenous neonatal administration of a self-complementary adeno-associated virus 9 vector (scAAV9) expressing the Hexb cDNA in SD mice is safe and sufficient to prevent disease development. Importantly, we demonstrate for the first time that this treatment results in a normal lifespan (over 700 days) and normalizes motor function assessed by a battery of behavioral tests, with scAAV9-treated SD mice being indistinguishable from wild-type littermates. Biochemical analyses in multiple tissues showed a significant increase in hexosaminidase A activity, which reached 10-15% of normal levels. AAV9 treatment was sufficient to prevent GM2 and GA2 storage almost completely in the cerebrum (less so in the cerebellum), as well as thalamic reactive gliosis and thalamocortical neuron loss in treated Hexb-/- mice. In summary, this study demonstrated a widespread protective effect throughout the entire CNS after a single intravenous administration of the scAAV9-Hexb vector to neonatal SD mice.

Topics: Administration, Intravenous; Animals; Animals, Newborn; Brain; Disease Models, Animal; Female; G(M2) Ganglioside; Gangliosides; Hexosaminidase B; Male; Mice; Mice, Inbred C57BL; Sandhoff Disease

2018

Recombinant GM2-activator protein stimulates in vivo degradation of GA2 in GM2 gangliosidosis AB variant fibroblasts but exhibits no detectable binding of GA2 in an in vitro assay.

Neurochemical research, 1999, Volume: 24, Issue:2

The interaction between glycosphingolipids and recombinant human GM2-activator was studied in a microwell binding assay. A-series gangliosides like GM3, GM2 and GM1 were strongly bound by the recombinant human GM2 activator. A weak binding was observed to GD1b and sulfatide, while neutral glycolipids were not bound. Optimal binding occurred at pH 4.2 and was inhibited by increasing concentrations of citrate buffer and NaCl. In contrast with these in vitro results the recombinant human GM2-activator is able to restore the degradation of GA2 in fibroblasts from patients with the AB variant of GM2 gangliosidosis in vivo.

Topics: Biotin; Cells, Cultured; Citrates; Fibroblasts; G(M2) Activator Protein; Gangliosides; Gangliosidoses; Glycosphingolipids; Humans; Hydrogen-Ion Concentration; Infant; Protein Binding; Proteins; Recombinant Proteins; Sandhoff Disease; Sodium Chloride; Tay-Sachs Disease

1999