Recombinant glucocerebrosidase (imiglucerase) as a therapy for Gaucher disease.

Imiglucerase is a recombinant formulation of human glucocerebrosidase, which is administered to patients with Gaucher disease (GD) as enzyme replacement therapy (ERT). Imiglucerase is generated from transduced Chinese hamster ovary cells, and modified by sequential deglycosylation of its carbohydrate side chains to expose alpha-mannosyl residues that mediate the uptake of the intravenously infused enzyme. The majority of patients initiate therapy on a fortnightly basis, using imiglucerase doses ranging from 30 to 60 U/kg bodyweight per infusion. Treatment has been shown to either stabilize or reverse several features of GD resulting from hematologic, visceral, and skeletal involvement. The treatment is well tolerated, and infusion-related adverse events such as pruritus and hives, observed primarily in patients who have developed antibodies to the exogenous enzyme, are readily managed. These findings have made ERT the standard of care for patients with GD type 1 (the non-neuronopathic form). Imiglucerase is also given to a majority of GD type 3 patients, as a means of assuaging their systemic problems. However, ERT has not been shown to eliminate the neurologic problems that these patients ultimately experience. Currently, two different enzyme formulations are in clinical trials. In addition, alternative therapeutic options are being explored as a substitute or complementary approach to ERT in the management of GD patients. The latter medications are oral agents that act to reduce substrate load either by inhibiting its synthesis or enhancing the residual activity of the endogenous mutant enzyme. Ongoing investigations are providing new insights into downstream mechanisms of disease, which may serve as further targets for adjunctive treatments. Cost of care considerations remain a topic of debate.