Alglucerase is a
mannose-terminated form of human placental
glucocerebrosidase, developed to treat patients with
Gaucher's disease. Functional
glucocerebrosidase is deficient in
Gaucher's disease, an autosomal recessive
lipid storage disorder that affects people of all ethnic backgrounds, but has a higher incidence among East European Jews (Ashkenazim).
Gaucher's disease manifests with hepatosplenomegaly,
bleeding disorders and
bone disease, with the more rare subtypes (types 2 and 3) featuring neurological dysfunction. Prior to the development of
enzyme replacement therapy, treatment for
Gaucher's disease was mainly symptomatic relief. Primary treatment with
glucocerebrosidase focuses on removal of the
lipid metabolite that causes the pathology. Because of the rarity of
Gaucher's disease clinical trials are small, and much of the data investigating
alglucerase therapy have been obtained from studies of patients with type 1 disease, the prevalent subtype. Nonetheless, after
intravenous administration of
alglucerase, improvements are evident within 6 months of
therapy. Patients have increased haemoglobin levels and platelet counts, and decreased incidences of
epistaxis and bruising. Spleen and liver size are reduced, and skeletal parameters improve. Children gain height and most patients receiving
alglucerase therapy are able to resume work and daily activities.
Alglucerase is well tolerated, with few mild adverse reactions reported. Although the pharmacokinetic and pharmacodynamic information for
alglucerase is limited, its unequivocal efficacy justifies
enzyme replacement therapy with this compound as first-line treatment for patients with
Gaucher's disease, for whom treatment options are limited.