BACKGROUND AND METHODS: Gaucher's disease, the most prevalent of the 
sphingolipid storage disorders, is caused by a deficiency of the enzyme 
glucocerebrosidase (glucosylceramidase). Enzyme replacement was proposed as a 
therapeutic strategy for this disorder in 1966. To assess the clinical 
effectiveness of this approach, we infused macrophage-targeted human placental 
glucocerebrosidase (60 IU per kilogram of body weight every 2 weeks for 9 to 12 
months) into 12 patients with type 1 Gaucher's disease who had intact spleens. 
The frequency of infusions was increased to once a week in two patients 
(children) during part of the trial because they had clinically aggressive 
disease.
RESULTS: The hemoglobin concentration increased in all 12 patients, and the 
platelet count in 7. Serum acid phosphatase activity decreased in 10 patients 
during the trial, and the plasma glucocerebroside level in 9. Splenic volume 
decreased in all patients after six months of treatment, and hepatic volume in 
five. Early signs of skeletal improvements were seen in three patients. The 
enzyme infusions were well tolerated, and no antibody to the exogenous enzyme 
developed.
CONCLUSIONS: Intravenous administration of macrophage-targeted 
glucocerebrosidase produces objective clinical improvement in patients with type 
1 Gaucher's disease. The hematologic and visceral responses to enzyme 
replacement develop more rapidly than the skeletal response.