ENZYME REPLACEMENT THERAPY BY FIBROBLAST TRANSPLANTATION - LONG-TERM BIOCHEMICAL STUDY IN 3 CASES OF HUNTERS SYNDROME

The effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy was assessed in 3 patients with Hunter''s syndrome, over periods ranging from 2.5-3.75 yr. The level of Hunter corrective factor excreted by all 3 patients increased after transplantation, as did the activity of .alpha.-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leucocyte homogenates from the 2 patients who were assessed. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by a decrease in sulfate:uronic ratios of urinary oligosaccharides, an increase in iduronic acid monosaccharide and a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.