Replacement Therapy for Inherited Enzyme Deficiency

TLDR

The study examined intravenous glucocerebrosidase from human placenta in two Gaucher disease patients lacking the enzyme. One patient received a single 1.5 × 10⁶‑unit injection, the other received 1.65 × 10⁶ units over two days, and liver biopsies were taken before and 24 h after infusion. Infusion lowered hepatic glucocerebroside from 702 to 519 µg/g and 1634 to 1214 µg/g, and reduced erythrocyte levels from 7.4/6.2 to 2.9/2.6 µg/ml, demonstrating that exogenous enzyme reduces lipid accumulation. Published in N Engl J Med 291:989–993, 1974.

Abstract

The effect of intravenous administration of glucocerebrosidase isolated from human placenta was investigated in two patients with Gaucher's disease who are deficient in this enzyme. The first received one injection of 1.5 x 106 units of glucocerebrosidase, and the second an injection of 1.65 x 106 units on two successive days. Liver biopsies were obtained before and 24 hours after injection of enzyme. Glucocerebroside in the liver of the first patient decreased from 702 to 519 μg per gram wet weight and from 1634 to 1214 μg per gram in the second after infusion of glucocerebrosidase. The quantity of glucocerebroside in erythrocytes of the two patients before infusion was 7.4 and 6.2 μg per milliliter of cells respectively and 2.9 and 2.6 μg per milliliter of cells 72 hours afterward. These findings indicate that exogenous glucocerebrosidase causes definite decreases in the quantity of accumulated lipid in patients with Gaucher's disease. (N Engl J Med 291:989–993, 1974)