Galactocerebrosidase (GALC) is deficient in all tissues from human patients and 
animal models with globoid cell leukodystrophy (GLD) or Krabbe disease. The 
deficiency results in decreased lysosomal catabolism of certain galactolipids 
including galactosylceramide and psychosine that are synthesized maximally 
during myelination. According to current theories, the accumulation of 
psychosine in humans and animals with GLD induces oligodendrocyte degeneration 
and myelination ceases. Transduction of oligodendrocytes from twitcher mice with 
a retroviral vector containing the GALC cDNA can correct the enzyme deficiency 
in these cells. Our data show that twitcher astrocytes and oligodendrocytes can 
internalize exogenous GALC, as well as donate the enzyme to the mutant glial 
cells. Antibodies against human GALC localized the GALC antigen in retrovirally 
transduced cells and cells receiving enzyme via cell to cell secretion and 
uptake to the lysosomal fraction. In fact immunocytochemical studies in 
transduced oligodendrocytes revealed that the GALC colocalizes in vesicles 
lysosomal-associated membrane protein-2 (LAMP2) (+). Moreover, labeling cells 
with anti-GALC and a marker for oligodendrocytes demonstrated that, upon 
differentiation, transduced, twitcher oligodendrocytes attained the normal 
branched process configuration, while untransduced cells show only abnormal 
morphology. Phenotype correction in mutant oligodendrocytes has also been 
observed after enzyme transfer. These studies indicate that GALC activity 
supplied to cultured oligodendrocytes from twitcher mice by different methods 
can correct the pathological phenotype of these cells.