Long-term effects of bone marrow transplantation on lysosomal enzyme replacement in beta-glucuronidase-deficient mice.

This study uses bone marrow transplantation (BMT) between congenic strains of mice as an experimental model to examine enzyme replacement therapy of lysosomal storage diseases. Bone marrow cells from donor mice which have normal levels of the lysosomal enzyme beta-glucuronidase (Gus), which is heat-stable, rapidly repopulated the haematopoietic compartment of irradiated recipient mice which have only low levels of a thermolabile form of this enzyme. Gus activity was found to increase progressively in the tissues of the recipients, including the liver, heart and skeletal muscle. Elevated levels were also observed in the kidney and brain. The increase in enzyme activity in the host tissues was not due to the presence of contaminating blood cells, but rather to the acquisition of new, heat-stable enzyme from the donor bone marrow cells. High levels of Gus activity persisted for at least 72 weeks, showing the potential therapeutic value of BMT for enzyme deficiency diseases.