Enzyme replacement therapy has been shown to be extraordinarily effective for patients with Type 1 (non-neuronopathic) Gaucher's disease. We are now developing procedures to deliver useful amounts of enzymes to the brain in patients with hereditary metabolic storage disorders. We have examined the effect of human placental beta-galactosidase on the amount of ganglioside GM1 in animal analogues of human generalized (GM1) gangliosidosis using a new intracerebral protein delivery system. We are also determining the distribution of glucocerebrosidase in the brain using convection-enhanced intracerebral injection of this enzyme. We are characterizing the receptors involved in the uptake of glucocerebrosidase and other enzymes by neurons in tissue culture.
