Description
Imiglucerase, a mannose-terminated form of human placental
glucocerebrosidase produced by recombinant technology, was introduced for the
treatment of type-1 Gaucher's disease. lmiglucerase catalyzes the hydrolysis of
glucocerebroside and thus prevents accumulation of this lipid in organs and tissues.
Compared with the natural enzyme, the modification by removal of the terminal
sugars resulted in strong binding of the exposed mannose to lectins expressed on
the surface of macrophages, which greatly increases the amount of enzyme taken
up by the cells. In 6-month clinical trials, its unequivocal efficacy was shown by
improvement in all patients with type-1 Gaucher's disease, leading to an increased
hemoglobin levels and platelet counts, decreased incidence of epistaxis and
bruising, reduced spleen and liver sizes, and improved skeletal parameters. This
enzyme replacement therapy is well tolerated with few mild adverse reactions.
Clinical Use
Type 1 Gaucher disease is a hereditary condition occurringin about 1:40,000 individuals. It is characterized by a functionaldeficiency in β-glucocerebrosidase enzyme activityand the resulting accumulation of lipid glucocerebroside intissue macrophages, which become engorged and aretermed Gaucher cells. Gaucher cells typically accumulate inthe liver, spleen, and bone marrow and, occasionally, inlung, kidney, and intestine. Secondary hematological sequelaeinclude severe anemia and thrombocytopenia in additionto characteristic progressive hepatosplenomegaly. Skeletalcomplications are common and are frequently the most debilitatingand disabling feature of Gaucher disease. Possibleskeletal complications are osteonecrosis, osteopenia withsecondary pathological fractures, remodeling failure, osteosclerosis,and bone crises.
Cerezyme (Imiglucerase) is a recombinant, macrophagetargetedvariant of human β-glucocerebrosidase, purified fromCHO cells. It catalyzes the hydrolysis of the glycolipid glucocerebrosideto glucose and ceramide following the normaldegradation pathway for membrane lipids.Cerezyme is supplied as a lyophilized powder for reconstitution.The powder should be stored at 2°C to 8°C untilused. The reconstituted product for IV infusion is stable for12 hours at room temperature.
