Retroviral-mediated transfer of the galactocerebrosidase gene in neural progenitor cells

GLOBOID cell leukodystrophy (GCL or Krabbe disease) is a recessive disease caused by mutations of the lysosomal enzyme galactocerebrosidase (GALC) and twitcher is the murine model of GCL. We have prepared retroviral packaging cell lines to transduce the GALC gene. Retroviral transduction restored GA LC activity in GCL fibroblasts and increased such activity to very high lev els in immortalized neural progenitor cells (ST14A cells). GALC activity wa s also normalized in twitcher fibroblasts co-cultured with ST14A cells over -expressing GALC, demonstrating that this enzyme is secreted and can be imp orted efficiently by GALC-deficient cells. These results give the necessary background to evaluate the therapeutic effect in twitcher of brain graftin g of neural progenitor cells engineered to release high levels of GALC. Neu roReport 9: 3823-3827 (C) 1998 Lippincott Williams & Wilkins.