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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Mar;87(5):1913–1916. doi: 10.1073/pnas.87.5.1913

Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease.

N W Barton 1, F S Furbish 1, G J Murray 1, M Garfield 1, R O Brady 1
PMCID: PMC53594  PMID: 2308952

Abstract

Enzyme replacement has been under consideration as a therapeutic strategy for patients with Gaucher disease for more than two decades. Previous studies indicated that single injections of purified glucocerebrosidase reduced the amount of storage material in the liver. It was important to determine whether administration of exogenous enzyme on a regular basis would be of clinical benefit. We report here that weekly i.v. infusions of a macrophage-targeted preparation of human placental glucocerebrosidase in a child with type 1 Gaucher disease increased hemoglobin from 6.9 +/- 0.8 g/dl (+/- 1 SD) to 10.2 +/- 0.4 g/dl (+/- 1 SD) over a 20-week period. The platelet count also increased from a pretreatment value of 30,000 +/- 7000/mm3 (+/- 1 SD) to 54,000 +/- 11,000/mm3 (+/- 1 SD). Phagocytic activity in the spleen decreased during the period of enzyme administration, and there was radiographic evidence of skeletal improvement. These observations document objective clinical responses to enzyme supplementation in a patient with a sphingolipid storage disorder.

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Selected References

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  1. Brady R. O., Pentchev P. G., Gal A. E., Hibbert S. R., Dekaban A. S. Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher's disease. N Engl J Med. 1974 Nov 7;291(19):989–993. doi: 10.1056/NEJM197411072911901. [DOI] [PubMed] [Google Scholar]
  2. Brady R. O. The sphingolipidoses. N Engl J Med. 1966 Aug 11;275(6):312–318. doi: 10.1056/NEJM196608112750606. [DOI] [PubMed] [Google Scholar]
  3. Furbish F. S., Blair H. E., Shiloach J., Pentchev P. G., Brady R. O. Enzyme replacement therapy in Gaucher's disease: large-scale purification of glucocerebrosidase suitable for human administration. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3560–3563. doi: 10.1073/pnas.74.8.3560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Furbish F. S., Steer C. J., Barranger J. A., Jones E. A., Brady R. O. The uptake of native and desialylated glucocerebrosidase by rat hepatocytes and Kupffer cells. Biochem Biophys Res Commun. 1978 Apr 14;81(3):1047–1053. doi: 10.1016/0006-291x(78)91456-0. [DOI] [PubMed] [Google Scholar]
  5. Furbish F. S., Steer C. J., Krett N. L., Barranger J. A. Uptake and distribution of placental glucocerebrosidase in rat hepatic cells and effects of sequential deglycosylation. Biochim Biophys Acta. 1981 Apr 3;673(4):425–434. doi: 10.1016/0304-4165(81)90474-8. [DOI] [PubMed] [Google Scholar]
  6. Kampine J. P., Brady R. O., Kanfer J. N., Feld M., Shapiro D. Diagnosis of gaucher's disease and niemann-pick disease with small samples of venous blood. Science. 1967 Jan 6;155(3758):86–88. doi: 10.1126/science.155.3758.86. [DOI] [PubMed] [Google Scholar]
  7. Larson S. M., Nelp W. B. Radiopharmacology of a simplifield technetium-99m-colloid preparation for photoscanning. J Nucl Med. 1966 Nov;7(11):817–826. [PubMed] [Google Scholar]
  8. Murray G. J. Lectin-specific targeting of lysosomal enzymes to reticuloendothelial cells. Methods Enzymol. 1987;149:25–42. doi: 10.1016/0076-6879(87)49041-1. [DOI] [PubMed] [Google Scholar]
  9. Stahl P. D., Rodman J. S., Miller M. J., Schlesinger P. H. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1399–1403. doi: 10.1073/pnas.75.3.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Takasaki S., Murray G. J., Furbish F. S., Brady R. O., Barranger J. A., Kobata A. Structure of the N-asparagine-linked oligosaccharide units of human placental beta-glucocerebrosidase. J Biol Chem. 1984 Aug 25;259(16):10112–10117. [PubMed] [Google Scholar]
  11. Tsuji S., Choudary P. V., Martin B. M., Winfield S., Barranger J. A., Ginns E. I. Nucleotide sequence of cDNA containing the complete coding sequence for human lysosomal glucocerebrosidase. J Biol Chem. 1986 Jan 5;261(1):50–53. [PubMed] [Google Scholar]

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