571 FAILURE OF FIBROBLAST ALLOGRAFT FOR ENZYME REPLACEMENT IN MUCOPOLYSACCHARIDOSIS, TYPE VI

Abstract

Subcutaneous transplantation of histocompatible cultured human fibroblasts in a hemizygote with mucopolysaccharidosis Type II, reportedly resulted in both clinical and biochemical improvement, the latter supported by increased uronic acid excretion (Dean et al. Nature 261:323, 1976). Therefore, we evaluated the effectiveless of fibroblast transplantation for enzyme replacement in an 8-year-old girl with arylsulfatase (AS) B deficiency, MPS Type VI. A suspension of cultured skin fibroblasts (3 × 108 cells) obtained from a histocompatible sister with normal ASB activity was administered subcutaneously to the recipient, followed by immuno-suppression with anti-thymocyte globulin. No rejection phenomena were observed. The activity of ASA and ASB in leukocytes, plasma, and urine, and the urinary excretion of total AMPS were determined pre- and post-transplantation. Clinical and pathological evaluation included assessment of changes in hepatosplenomegaly, long bone growth, and ultrastructural accumulation of conjunctival AMPS. These biochemical, ultrastructural, and clinical parameters were unaltered up to 9 months after transplantation. The failure of fibroblasts to synthesize sufficient ASB activity to effect a biochemical or clinical change may be due to insufficient cell dose, homograft rejection, or, more likely, the inability of the infused cells to produce and distribute active and stable enzyme for AMPS degradation.