ENZYME REPLACEMENT THERAPY FROM BIRTH IN A FELINE MODEL OF MUCOPOLYSACCHARIDOSIS TYPE-VI

We report evidence of a dose responsive effect of enzyme replacement t herapy in mucopolysaccharidosis type VI cats from birth, at the clinic al, biochemical, and histopathological level. Cats treated with weekly , intravenous recombinant human N-acetylgalactosamine-4-sulfatase at 1 and 5 mg/kg, were heavier, more flexible, had greatly reduced or no s pinal cord compression, and had almost normal urinary glycosaminoglyca n levels. There was near normalization or complete reversal of lysosom al storage in heart valve, aorta, skin, dura, liver, and brain perivas cular cells. No reduction in lysosomal vacuolation was observed in car tilage or cornea; however, articular cartilage was thinner and externa l ear pinnae were larger in some treated cats. Degenerative joint chan ges were not obviously delayed in treated cats. Skeletal pathology was reduced, with more normalized bone dimensions and with more uniform b one density and trabecular pattern clearly visible on radiographs by 5 to 6 mo; however, differences between 1 and 5 mg/kg dose rates were n ot clearly distinguishable. At a dose of 0.2 mg/kg, disease was not si gnificantly altered in the majority of parameters examined. Lysosomal storage was present in all tissues examined in the midterm mucopolysac charidosis type VI fetus and increased rapidly in extent and severity from birth.