Extraordinarily gratifying success has been obtained with enzyme replacement therapy in patients with Gaucher's disease. All patients who received macrophage-targeted human placental glucocerebrosidase had significant clinical benefit. The hemoglobin level rose in all patients, and the size of the spleen and liver decreased in all recipients. Long- term treatment has produced reversal of skeleton pathology. Patients who received the enzyme were able to resume activities such as work or school that they had been unable to carry out before enzyme replacement. The U.S. Food and Drug Administration has approved the use of macrophage- targeted glucocerebrosidase as specific therapy for patients with Type 1 Gaucher's disease. The beneficial effect of enzyme replacement in patients with Gaucher's disease has been repeatedly confirmed. The quantity of enzyme that patients require to be maintained in good health is far less than that which is initially necessary to reverse the clinical and pathological manifestations of the disorder. Patients with milder clinical signs of the disorder improve with smaller amounts of enzyme than that required by more severely affected individuals. Recombinantly produced macrophage-targeted glucocerebrosidase has been found to be as effective as the placental enzyme used in the original clinical efficacy trial. A series of investigations is currently in progress to determine the effects of enzyme replacement therapy on the nervous system in patients with neuronopathic forms of Gaucher's disease. We have demonstrated the delivery of small amounts of enzyme to the nervous system in these patients and are currently analyzing its effects on neurophysiologic parameters and biochemical markers in the cerebrospinal fluid. The outcome of these investigations will significantly influence therapeutic strategies for many inherited metabolic disorders of the nervous system. In addition, we have begun a Phase 1 gene therapy trial in patients with Type 1 (non-neuronopathic) Gaucher's disease.
