MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII - LONG-TERM THERAPEUTIC EFFECTSOF ENZYME REPLACEMENT AND ENZYME REPLACEMENT FOLLOWED BY BONE-MARROW TRANSPLANTATION

We demonstrated previously that short term administration of recombina nt beta-glucuronidase to newborn mice with mucopolysaccharidosis type VII reduced lysosomal storage in many tissues, Lysosomal storage accum ulated gradually after cessation of enzyme replacement therapy, Mice a live at 1 yr of age had decreased bone deformities and less lysosomal storage In cortical neurons, Here we compare the effects of long term enzyme replacement initiated either at birth or at 6 wk of age, and of enzyme administration initiated at birth followed by syngeneic bone m arrow transplantation (BMT) at 5 wk of age, Several mice from each tre atment group lived to at least 1 pr of age, Liver and spleen samples h ad beta-glucuronidase levels ranging from 2.4 to 19.8% of normal and s howed a parallel decrease in lysosomal storage, The combination of enz yme replacement therapy followed by EMT reduced lysosomal distension i n meninges, corneal fibroblasts, and bone when compared with treatment with enzyme alone, Mice treat-ed at birth had less lysosomal storage in some neurons of the brain and the skeletal dysplasia was less sever e when compared to mice whose treatment was delayed until 6 wk of age, We conclude that both enzyme replacement alone and early enzyme repla cement followed by BMT have long term positive effects on murine mucop olysaccharidosis type VII, In addition, treatment started at birth is far more effective than treatment initiated in young adults.