GENE-THERAPY FOR MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII

Mucopolysaccharidosis type VII (MPS VII) is caused by a deficiency in the lysosomal enzyme beta-glucuronidase resulting in the accumulation of undegraded glycosaminoglycans in many tissues. A murine model of MP S VII shares many of the clinical, biochemical and histopathological f eatures of human MPS VII and has provided an opportunity to study nove l therapeutic approaches in a system with a uniform genetic background . Retroviral mediated gene therapy directed to the hematopoietic syste m or to artificial neo-organs resulted in low levels of enzyme in seve ral tissues and reduced lysosomal storage in the liver and spleen. Par tial correction of the disease in the eye was observed following an in travitreal injection of recombinant adenovirus. Neither retroviral nor adenoviral mediated gene transfer techniques resulted in a systemic r eduction of lysosomal storage. Here we discuss several novel gene tran sfer approaches designed to increase the systemic levels of beta-glucu ronidase in the MPS VII mouse. (C) 1997 Elsevier Science B.V.