Replacement Therapy for Inherited Enzyme Deficiency — Macrophage-Targeted Glucocerebrosidase for Gaucher's Disease

• Published in: The New England journal of medicine Vol. 324; no. 21; pp. 1464 - 1470
• Main Authors: Barton, Norman W, Brady, Roscoe O, Dambrosia, James M, Di Bisceglie, Adrian M, Doppelt, Samuel H, Hill, Suvimol C, Mankin, Henry J, Murray, Gary J, Parker, Robert I, Argoff, Charles E, Grewal, Raji P, Yu, Kian-Ti
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 23.05.1991
• Subjects: Abdomen; Acid phosphatase; Acid Phosphatase - blood; Acids; Adolescent; Adult; Biological and medical sciences; Blood platelets; Blood tests; Body weight; Bone Development - drug effects; Child; Children; Electrocardiography; Enzymes; Female; Fibroblasts; Gaucher Disease - drug therapy; Gaucher's disease; General and cellular metabolism. Vitamins; glucocerebrosidase; Glucosylceramidase; Glucosylceramidase - administration & dosage; Glucosylceramidase - therapeutic use; Glucosylceramides - blood; Hemoglobin; Hemoglobins - analysis; Hepatitis; HIV; Human immunodeficiency virus; Humans; Intravenous administration; Iron; Laboratories; Lipids; Macrophages; Macrophages - drug effects; Male; Medical research; Medical sciences; Metabolism; Neurological disorders; NMR; Nuclear magnetic resonance; Organ Size; Pharmacology. Drug treatments; Phosphatase; Placenta; Plasma; Radiography; Regression analysis; Spleen; Spleen - pathology; Human; Replacement therapy; Enzyme; Deficiency; Lipids; Metabolic diseases; Genetic disease; Case study; Chemotherapy; Gaucher disease; Drug targeting; Glucosylceramidase; Macrophage
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM199105233242104

GAUCHER'S disease is the most prevalent lysosomal storage disorder. It is caused by an insufficiency of glucocerebrosidase (glucosylceramidase) activity 1 , 2 with secondary accumulation of glucocerebroside within the lysosomes of macrophages. The storage disorder produces a multisystem disease characterized by progressive visceral enlargement and gradual replacement of the bone marrow with lipid-laden macrophages. Symptomatic anemia, coagulation abnormalities, visceral enlargement, and structural skeletal changes occur at some point during the course of the illness in most patients. Progressive neurologic deterioration develops in a minority. 3 , 4 Enzyme replacement was proposed as a therapeutic strategy for Gaucher's disease in 1966. 5 It was demonstrated in 1974 that . . .