Abstract
Following the discovery that insufficient activity of glucocerebrosidase was the metabolic defect in Gaucher disease, attention was directed to the possibility that the health of patients might be improved by the administration of purified exogenous enzyme. Glucocerebrosidase for this investigation was originally obtained from human placental tissue. Intravenous administration of this enzyme to patients with Gaucher disease reduced the amount of accumulated glucocerebroside in the liver and circulation. Enzyme subsequently obtained by a large-scale purification procedure required modification of its glycoform for the successful treatment of patients with Gaucher disease. The steps involved in this endeavor and benefit of appropriately modified glucocerebrosidase for patients with Gaucher disease are chronicled.
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References
Aghion A (1934) La maladie de Gaucher dans l’enfance. Thèse, Paris
Barton NW, Furbish FS, Murray GJ, Garfield M, Brady RO (1990) Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A 87:1913–1916
Barton NW, Brady RO, Dambrosia JM, DiBisceglie AM, Doppelt SH, Hill SC, Mankin HJ, Murray GJ, Parker RI, Argoff CE, Grewal RP, Yu K-T (1991) Replacement therapy for inherited enzyme deficiency—macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med 324:1464–1470
Brady RO (1966) The sphingolipidoses. N Engl J Med 275:312–318
Brady RO, Furbish FS (1982) Enzyme replacement therapy: specific targeting of exogenous enzymes to storage cells. In: Martonosi AN (ed) Membranes and transport, vol 2. Plenum, New York, pp 587–592
Brady RO, Kanfer J, Shapiro D (1965a) The metabolism of glucocerebrosides. I. Purification and properties of a glucocerebroside-cleaving enzyme from spleen tissue. J Biol Chem 240:39–42
Brady RO, Kanfer JN, Shapiro D (1965b) The metabolism of glucocerebrosides. II. Evidence of an enzymatic deficiency in Gaucher’s disease. Biochem Biophys Res Commun 18:221–225
Brady RO, Kanfer JN, Bradley RM, Shapiro D (1966) Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher’s disease. J Clin Invest 45:1112–1115
Brady RO, Pentchev PG, Gal AE, Hibbet SR, Dekaban AS (1974) Replacement therapy for inherited enzyme deficiency: use of purified glucocerebrosidase in Gaucher’s disease. N Engl J Med 291:989–993
Brill NE (1901) Primary splenomegaly with a report of three cases occurring in one family. Am J Med Sci 121:377–392
Choy FYM (1984) Gaucher disease: the effects of phosphaticylserine on glucocerebrosidase from normal and Gaucher fibroblasts. Hum Genet 67:432–436
Dale GL, Villacorte DG, Beutler E (1976) Solubilization of glucocerebrosidase from human placenta and demonstration of a phospholipid requirement for its catalytic activity. Biochem Biophys Res Commun 71:1048–1053
Furbish FS, Blair HE, Shiloach J, Pentchev PG, Brady RO (1977) Enzyme replacement therapy in Gaucher’s disease: large-scale purification of glucocerebrosidase suitable for human administration. Proc Natl Acad Sci U S A 74:3560–3563
Furbish FS, Steer CJ, Barranger JA, Jones EA, Brady RO (1978) The uptake of native and desialylated glucocerebrosidase by rat hepatocytges and Kupffer cells. Biochem Biophys Res Commun 81:1047–1053
Furbish FS, Steer CJ, Krett NL, Barranger JA (1981) Uptake and distribution of placental glucocerebrosidase in rat hepatic cells and effects of sequential deglycosylation. Biochim Biophys Acta 673:425–434
Gaucher PCE (1882) De l’épithélioma primitif de la rate. Thèse de Paris
Grabowski GA, Barton NW, Pastores G, Dambrosia JM, Banerjee TK, McKee MA, Parker C, Schiffmann R, Hill SC, Brady RO (1995) Enzyme therapy in Gaucher disease type 1: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med 122:33–39
Lieb H (1924) Cerebrosidespeicherung bei Splenomegalie Typus Gaucher. Ztschr Physiol Chem 140:305–313
Marchand F (1907) Über Sogennante idiopathische Splenomegalie (Typus Gaucher). Munchen med Wchnschr 54:1102–1103
Pentchev PG, Brady RO, Hibbert SR, Gal AE, Shapiro D (1973) Isolation and characterization of glucocerebrosidase from human placental tissue. J Biol Chem 248:5256–5261
Pentchev PG, Brady RO, Gal AE, Hibbert SR (1975) Replacement therapy for inherited enyzme deficiency. Sustained clearance of accumulated glucocerebroside in Gaucher’s disease following infusion of purified glucocerebrosidase. J Mol Med 1:73–78
Schroit AJ, Tanaka Y, Madsen J, Fidler IJ (1984) The recognition of red blood cells by macrophages: role of phosphatidylserine and possible implications of membrane phospholipid asymmetry. Biol Cell 51:227–238
Stahl PD, Rodman JS, Miller MJ, Schlesinger PH (1978) Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A 75:1399–1403
Steer CJ, Furbish FS, Barranger JA, Brady RO, Jones EA (1978) The uptake of agalacto-glucocerebrosidase by rat hepatocytes and Kupffer cells. FEBS Lett 91:202–205
Takasaki S, Murray GJ, Furbish F, Brady RO, Barranger JA, Kobata A (1984) Structure of N-asparagine-linked oligosaccharide units of human placental beta-glucocerebrosidase. J Biol Chem 259:10112–10117
Trams EG, Brady RO (1960) Cerebroside synthesis in Gaucher’s disease. J Clin Invest 39:1546–1550
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Brady, R.O. (2015). Targeting Glucocerebrosidase to Macrophages for Effective Treatment of Patients with Gaucher Disease: Setting the Paradigm of a “Fit for Purpose” Approach to Enzyme Replacement Therapy. In: Rosenberg, A., Demeule, B. (eds) Biobetters. AAPS Advances in the Pharmaceutical Sciences Series, vol 19. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2543-8_1
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