Enzyme replacement therapy by fibroblast transplantation. Long-term biochemical study in three cases of Hunter's syndrome

Abstract

The authors assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunter's syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of α-L-idurono-2-sulfate in serum, when measured directly with radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that the authors were able to assess. These increases in the enzyme activity were acccompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrase in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization in Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.