A clinical trial of fibroblast transplantation for the treatment of mucopolysaccharidoses

Abstract

This paper reports the clinical and biochemical results in six patients with Hurler disease (Mucopolysaccharidosis IH; McKusick 25280), two patients with Hunter disease (Mucopolysaccharidosis II; McKusick 25285) and one patient with Sanfilippo B disease (Mucopolysaccharidosis IIIB; McKusick 25292) who were treated by fibroblast transplantation. Except for one patient who died for a coincidental reason, the patients have been studied for between 2.5 and 4.5 years. The clinical course of the disease was not materially altered. There was no evidence that the patients had developed immune responses against the transplanted fibroblasts. Transplantation did not produce measurable levels of either alpha-L-iduronidase (EC 3.2.1.76) in the leukocytes from patients with Hurler disease or of N-acetyl-alpha-D-glucosaminidase (EC 3.2.1.50) in the plasma of the patients with Sanfilippo B disease. Under the conditions used for the assay, leukocytes from the patients with Hunter disease had detectable levels of residual alpha-L-idurono-2-sulphate sulphatase activity which were increased after the transplants, although these changes were of inconstant size and their time course was not consistently related to the transplantations. Cytogenetic studies in cases where the donor was of the opposite sex detected only cells of the recipient's sex among the fibroblasts grown from biopsies of the transplantation sites. The technique used would have detected a donor to recipient cell ratio of 1:100. We found no consistent long-term trends in the excretion patterns of glycosaminoglycans and oligosaccharides from either a quantitative or qualitative point of view which could be specifically related to the transplantation. The combined administration of immunosuppressive doses of prednisolone and azathioprine was associated with an increased excretion of the lower molecular weight glycosaminoglycans. We conclude that fibroblast transplantation is not therapeutically useful in the diseases studied.

Attempted enzyme replacement using human amnion membane implantations in mucopolysaccharidoses

“…A moderate shift toward normal in excretion of urinary mucopolysaccharides was also detected, but patients experienced no convincing clinical change. Gibbs et al (1983) also reported that fibroblast transplantation in MPS I, MPS II and MPS III was not therapeutically useful.…”

A historical perspective of the glycosphingolipids and sphingolipidoses

“…This led to attempts to treat lysosomal storage diseases by systemic cell implantation. An early attempt using cultured histocompatible fibroblasts (Gibbs et al 1983) in some of the mucopolysaccharidoses was unsuccessful. Bone marrow transplantation has been tried on the premise that engrafted bone marrow would produce large numbers of exocytic cells that would circulate and transfer their normal enzyme to enzyme-deficient cells (see Krivit & Paul 1986).…”

Low arylsulphatase A activity and choreoathetotic syndrome in three siblings: differentiation of pseudodeficiency from metachromatic leukodystrophy

“…They all looked normal except for the manifestations of disordered motor function. Patients 1 and 2 were given subcutaneous implants of fibroblasts [8] without appreciable overall improvement or deterioration during this period.…”