LONG-TERM ENZYME REPLACEMENT THERAPY IN BETA-GLUCURONIDASE DEFICIENT MICE BY ALLOGENEIC BONE-MARROW TRANSPLANTATION

  • 1 January 1982
    • journal article
    • research article
    • Vol. 99  (6) , 792-797
Abstract
Enzyme replacement therapy was successfully accomplished in .beta.-Glu[.beta.-glucuronidase]-deficient C3H/HeJ mice after transplantation of BM [bone marrow] cells obtained from normal BALB/c donors. Marrow recipients were prepared for transplantation by fractionated TLI [total lymphoid irradiation]. Enzyme activity increased from 20.5 .+-. 7.0 nmol/mg of protein per h to 180 .+-. 30.2 in the liver (P < 0.001) and from 8.2 .+-. 2.0 to 17.5 .+-. 5.0 nmol/ml per h in the plasma (P < 0.05) at 50 days after marrow infusion. Normal enzyme activity was maintained in treated mice for at least 100 days after marrow transplantation, as documented by repeated liver biopsies and examination of plasma samples. The marrow donors and the recipients were fully histoincompatible. Both immumnologic rejection of the marrow allograft and GVHD [graft vs. host disease] were prevented by the prior conditioning of the recipients with TLI, resulting in bilateral transplantation tolerance of host vs. graft and graft vs. host. Allogeneic BM transplantation may provide a possible therapeutic approach for certain enzyme deficiency syndromes.