Mucopolysaccharidosis (MPS) type VII (OMIM 253220) is a progressive neurometabolic disorder caused by deficiency of the lysosomal enzyme β-glucuronidase (GUS).
The non-viral, integrating Sleeping Beauty (SB) transposon system is efficient in treating systemic monogenic disease in mice, including hemophilia A and B caused by deficiency of blood clotting factors and mucopolysaccharidosis types I and VII caused by α-L-iduronidase (IDUA) and β-glucuronidase (GUSB) deficiency, respectively.
We sought to identify human β-glucuronidase variants that display α-iduronidase activity, which is defective in mucopolysaccharidosis (MPS) type I patients.
A deficiency of beta-glucuronidase (GUSB) causes the multisystem progressive degenerative syndrome, mucopolysaccharidosis (MPS) type VII (Sly disease), which includes mental retardation.Animal homologues of MPS VII (ref.
An in vitro model for cross-correction of lysosomal storage disorders from genetically modified cells was developed to approximate the physiological conditions needed for gene therapy in vivo. beta-Glucuronidase (GUSB)-deficient mucopolysaccharidosis (MPS) type VII (Sly disease) cells were studied to determine the amount and stability of enzyme transfer.
These findings demonstrate that the GUSB transgene is expressed in gusmps/gusmps mice and that human beta-glucuronidase corrects the murine mucopolysaccharidosis storage disease.
The phenotypic variation and the fact that increased levels of glycosaminoglycans were not found in the urine of the two patients lead to the suggestion that in certain cases a correct diagnosis may be missed if the beta-glucuronidase activity in plasma and leucocytes is not determined and only routine urine investigation is performed as a screening for a mucopolysaccharidosis.