Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153470 (Spleen)
 4,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Alglucerase. A review of its therapeutic use in Gaucher's disease. 137 12

Gaucher disease is caused by a deficiency of glucocerebrosidase. It is the first lysosomal storage disorder for which effective enzyme-supplementation therapy has become available. The enzyme, alglucerase, is glucocerebrosidase derived from human placental tissue; its oligosaccharide chain has been modified to expose terminal mannose residues, facilitating uptake in macrophages. Many patients have been shown to benefit from treatment with the enzyme. Spleen and liver volumes decrease and cytopenia improves. Over a longer period of time, bone involvement can also be diminished, although severe pre-existing bone abnormalities do not change. The safety profile of alglucerase seems excellent, with only few adverse events and approximately 12% of patients developing antibodies. Because long term safety is unknown and the enzyme is very expensive, studies have focused on the determination of the optimum individual dosage. Different dosages have shown to be effective, but so far the identification of patients who need a high or a low dosage is unclear. Other issues that deserve attention are the selection criteria for the initiation of treatment and the place of prophylactic treatment. Diversity in the course of the disease, which in many cases cannot be predicted by genotyping, hampers the establishment of strict rules. Multicentre studies, in which comparison of data is made possible by the use of standardised measurements of disease manifestations, may be needed to solve these issues.
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PMID:Alglucerase: practical guidance on appropriate dosage and administration in patients with Gaucher disease. 1802 May 53