Macrophage targeted glucocerebrosidase

Barton, N. W., Brady, R. O., Dambrosia, J. M. et al. Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher s disease. N. Engl. J. Med. 324 1464-1470,1991. 

Medicine in New York using glucocerebrosidase that had been produced lecont-binantly in Chinese hamster ovary cells. The enzyme obtained from these cells was modified by exposure to the- same these cxogtycosidases used previously to produce mannose-terminal placental glucoceiebrosidase (Kg, 2). The clinical effectiveness of the recombinant macrophage-targeted enzyme was found to be... 

IV. FIRST DEMONSTRATION OF CLINICAL RESPONSES TO MACROPHAGE-TARGETED GLUCOCEREBROSIDASE... 

Significant reductions in hepatic glucocerebroside content occurred in 8 of 11 patients with intact spleens who underwent liver biopsy before and 44 hours after receiving enzyme doses between 30 and 234 U/kg body weight infused over 4 hours. In contrast, a reduction in lipid level was observed in only 1 of 10 patients who received doses between 0.6 and 24 U/kg. Specific activity measurements in liver biopsy specimens obtained 44 hours after infusion of macrophage-targeted glucocerebrosidase were compatible with a cellular elimination half-life... 

Table 2 Hematological Responses to Macrophage-Targeted Glucocerebrosidase Time Course and Effects of Dosage Reduction...

Figure 12 Photograph of an 8-year-old girl with Gaucher disease before (PRE) and after (POST) 26 months of treatment with macrophage-targeted glucocerebrosidase at a dose of 60 U/kg every 2 weeks. Marked reduction in visceromegaly is evident.

Table 5 Effects of Enzyme Dosage on Hematological and Visceral Responses to Macrophage-Targeted Glucocerebrosidase...

K. A. McKusick, B. R. Rosen, J. Baker, L. T. Niklason, S. C. Hill, S. P. F. Miller, R. O. Brady, and N. W. Barton. Enzyme replacement therapy for Gaucher s disease skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics 96 629 (1995). 

S. M. Richards, T. A. Olson, and J. M. McPherson. Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. Blood 82 1402(1993). 

The adult form of Gaucher disease (type I) is currently the only sphingolipid storage disease for which a causal therapy is available [33]. The patients are treated with a modified glucocerebrosidase from human placenta or a recombinant sample. The protein carbohydrates contain the targeting information for the mannose receptor on macrophages. 

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