Imiglucerase in the treatment of Gaucher disease: A history and perspective

Drug Design, Development and Therapy

Volumn 6, Issue , 2012, Pages 81-106

  Deegan, Patrick B ^a   Cox, Timothy M ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Biopharmaceutical; Enzyme therapy; Lysosomal disease; Macrophage targeting; Mannose lectin; Ultra orphan

Indexed keywords

ALGLUCERASE; BISPHOSPHONIC ACID DERIVATIVE; CARBOHYDRATE; ELIGLUSTAT; GLUCOSYLCERAMIDASE; IMIGLUCERASE; MIGLUSTAT; TALIGLUCERASE ALFA; VELAGLUCERASE ALFA;

CARBOHYDRATE ANALYSIS; CLINICAL FEATURE; COST EFFECTIVENESS ANALYSIS; DELAYED PUBERTY; DIARRHEA; DOSE RESPONSE; DRUG BLOOD LEVEL; DRUG COST; DRUG HYPERSENSITIVITY; DRUG INDUSTRY; DRUG MANUFACTURE; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME REPLACEMENT; GAUCHER DISEASE; GBA1 GENE; GENE; HEALTH CARE ACCESS; HEPATOSPLENOMEGALY; HUMAN; HURLER SYNDROME; HYPERSPLENISM; IN VIVO STUDY; INTERSTITIAL LUNG DISEASE; LIFE EXPECTANCY; MACROPHAGE FUNCTION; NONHUMAN; OUTCOME ASSESSMENT; PANCYTOPENIA; PATHOPHYSIOLOGY; PERIPHERAL NEUROPATHY; PREGNANCY; REVIEW; SIDE EFFECT; SPLENOMEGALY; TREMOR; WEIGHT REDUCTION;

EID: 84863746895     PISSN: 11778881     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (172)

1. Barton NW, Furbish FS, Murray GJ, Garfield M, Brady RO. Therapeutic response to intravenous infusions of glucocerebrosidase in a patient with Gaucher disease. Proc Natl Acad Sci U S A. 1990;87(5):1913-1916.
2. Barton NW, Brady RO, Dambrosia JM, et al. Dose-dependent responses to macrophage-targeted glucocerebrosidase in a child with Gaucher disease. J Pediatr. 1992;120(2 Pt 1):277-280.
3. Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med. 1991;324(21): 1464-1470.
4. Grabowski GA, Petsko GA, Kolodny EH. Gaucher disease. Available from: http://www.ommbid.com/OMMBID/the_online_metabolic_ and_molecular_bases_of_inherited_disease/b/abstract/part16/ch146. Accessed January 20, 2012.
5. Futerman AH. Cellular pathology in Gaucher disease. In: Futerman AH, Zimran A, editors. Gaucher Disease. Vol 1. Boca Raton (FL): CRC Press; 2007:97-108.
6. Meikle PJ, Hopwood JJ, Clague AE, Carey WF. Prevalence of lysosomal storage disorders. JAMA. 1999;281(3):249-254.
7. Meikle PJ, Fuller M, Hopwood JJ. Epidemiology and screening policy. In: Futerman AH, Zimran A, editors. Gaucher Disease. Vol 1. Boca Raton (FL): CRC Press; 2007:321-340.
8. Grabowski GA. Gaucher disease: gene frequencies and genotype/ phenotype correlations. Genet Test. 1997;1(1):5-12.
9. Conradi N, Kyllerman M, Mansson JE, Percy AK, Svennerholm L. Late-infantile Gaucher disease in a child with myoclonus and bulbar signs: neuropathological and neurochemical findings. Acta Neuropathol. 1991;82(2):152-157.
10. Biegstraaten M, Mengel E, Maródi L, et al. Peripheral neuropathy in adult type 1 Gaucher disease: a 2-year prospective observational study. Brain. 2010;133(10):2909-2919.
11. Neudorfer O, Giladi N, Abrahamov A, et al. Occurrence of Parkinson's syndrome in type I Gaucher disease. QJM. 1996;89(9):691-694.
12. Koprivica V, Stone DL, Park JK, et al. Analysis and classification of 304 mutant alleles in patients with type 1 and type 3 Gaucher disease. Am J Hum Genet. 2000;66(6):1777-1786.
13. Hruska KS, Lamarca ME, Sidransky E. Gaucher disease: Molecular biology and genotype-phenotype correlations. In: Futerman AH, Zimran A, editors. Gaucher Disease. Boca Raton, FL: Taylor & Francis; 2006: 13-48.
14. Abrahamov A, Elstein D, Gross-Tsur V, et al. Gaucher's disease variant characterised by progressive calcification of heart valves and unique genotype. Lancet. 1995;346(8981):1000-1003.
15. Chabas A, Cormand B, Grinberg D, et al. Unusual expression of Gaucher's disease: cardiovascular calcifications in three sibs homozygous for the D409H mutation. J Med Genet. 1995;32(9):740-742.
16. Locatelli Hoops S, Kolter T, Sandhoff K. Saposin C and other sphingolipid activator proteins. In: Futerman A, Zimran A, editors. Gaucher Disease. Vol 1. Boca Raton (FL): CRC Press; 2007:67-84.
17. Nilsson O, Hakansson G, Dreborg S, Groth CG, Svennerholm L. Increased cerebroside concentration in plasma and erythrocytes in Gaucher disease: significant differences between type I and type III. Clin Genet. 1982;22(5):274-279.
18. Nilsson O, Mansson JE, Hakansson G, Svennerholm L. The occurrence of psychosine and other glycolipids in spleen and liver from the three major types of Gaucher's disease. Biochim Biophys Acta. 1982; 712(3):453-463.
19. Nilsson O, Svennerholm L. Accumulation of glucosylceramide and glucosylsphingosine (psychosine) in cerebrum and cerebellum in infantile and juvenile Gaucher disease. J Neurochem. 1982;39(3):709-718.
20. Lee RE. The pathology of Gaucher disease. Prog Clin Biol Res. 1982;95:177-217.
21. Lee RE. Pathologic anatomy of Gaucher disease: a pictorial essay. In: Futerman AH, Zimran A, eds. Gaucher Disease. Boca Raton: CRC Press; 2007:197-224.
22. Boven LA, van Meurs M, Boot RG, et al. Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages. Am J Clin Pathol. 2004;122(3):359-369.
23. Cox TM. Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. J Inherit Metab Dis. 2001;24 Suppl 2:106-121; discussion 87-88.
24. Mistry P, Zimran A. Type 1 Gaucher disease-clinical features. In: Futerman AH, Zimran A, editors. Gaucher Disease. Vol 1. Boca Raton (FL): CRC Press; 2007:155-173.
25. Deegan PB, Pavlova E, Tindall J, et al. Osseous manifestations of Gaucher disease in the era of enzyme replacement. Medicine (Baltimore). 2011;90(1):52-60.
26. Mistry PK, Weinreb NJ, Kaplan P, Cole JA, Gwosdow AR, Hangartner T. Osteopenia in Gaucher disease develops early in life: response to imiglucerase enzyme therapy in children, adolescents and adults. Blood Cells Mol Dis. 2011;46(1):66-72.
27. Allen MJ, Myer BJ, Khokher AM, Rushton N, Cox TM. Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10. QJM. 1997;90(1): 19-25.
28. Moran MT, Schofield JP, Hayman AR, Shi GP, Young E, Cox TM. Pathologic gene expression in Gaucher disease: up-regulation of cysteine proteinases including osteoclastic cathepsin K. Blood. 2000;96(5):1969-1978.
29. Grafe M, Thomas C, Schneider J, Katz B, Wiley C. Infantile Gaucher's disease: a case with neuronal storage. Ann Neurol. 1988;23(3): 300-303.
30. Conradi NG, Sourander P, Nilsson O, Svennerholm L, Erikson A. Neuropathology of the Norrbottnian type of Gaucher disease: morphological and biochemical studies. Acta Neuropathol. 1984;65(2):99-109.
31. Prabakaran T, Nielsen R, Larsen JV, et al. Receptor-mediated endocytosis of o-galactosidase A in human podocytes in Fabry disease. PLoS One. 2011;6(9):e25065.
32. Reczek D, Schwake M, Schroder J, et al. LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase. Cell. 2007;131(4):770-783.
33. Cox TM, Schofield JP. Gaucher's disease: clinical features and natural history. Baillieres Clin Haematol. 1997;10(4):657-689.
34. Biegstraaten M, van Schaik IN, Aerts JM, et al. A monozygotic twin pair with highly discordant Gaucher phenotypes. Blood Cells Mol Dis. 2011;46(1):39-41.
35. Lachmann RH, Grant IR, Halsall D, Cox TM. Twin pairs showing discordance of phenotype in adult Gaucher's disease. QJM. 2004;97(4):199-204.
36. Tajima A, Yokoi T, Ariga M, et al. Clinical and genetic study of Japanese patients with type 3 Gaucher disease. Mol Genet Metab. 2009;97(4):272-277.
37. Jeong SY, Park SJ, Kim HJ. Clinical and genetic characteristics of Korean patients with Gaucher disease. Blood Cells Mol Dis. 2011;46(1): 11-14.
38. Ida H, Iwasawa K, Kawame H, Rennert OM, Maekawa K, Eto Y. Characteristics of gene mutations among 32 unrelated Japanese Gaucher disease patients: absence of the common Jewish 84GG and 1226G mutations. Hum Genet. 1995;95(6):717-720.
39. Rice EO, Mifflin TE, Sakallah S, Lee RE, Sansieri CA, Barranger JA. Gaucher disease: studies of phenotype, molecular diagnosis and treatment. Clin Genet. 1996;49(3):111-118.
40. Kaplan P, Andersson HC, Kacena KA, Yee JD. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis. Arch Pediatr Adolesc Med. 2006;160(6): 603-608.
41. Lachmann RH, Wight DG, Lomas DJ, et al. Massive hepatic fibrosis in Gaucher's disease: clinico-pathological and radiological features. QJM. 2000;93(4):237-244.
42. Kelsey H, Christopoulos C, Gray AA, Machin SJ. Acquired pseudopseudo Bernard-Soulier syndrome complicating Gaucher's disease. J Clin Pathol. 1994;47(2):162-165.
43. Simchen MJ, Oz R, Shenkman B, Zimran A, Elstein D, Kenet G. Impaired platelet function and peripartum bleeding in women with Gaucher disease. Thromb Haemost. 2011;105(3):509-514.
44. Coyne JD, Lynch T, Cotter P, Kealy WF, Duggan PF. Gaucher's disease: a case report with coincidental vitamin B12 deficiency anaemia. Ir Med J. 1985;78(9):254-255.
45. Gielchinsky Y, Elstein D, Green R, et al. High prevalence of low serum vitamin B12 in a multi-ethnic Israeli population. Br J Haematol. 2001;115(3):707-709.
46. Fleshner PR, Aufses AH Jr, Grabowski GA, Elias R. A 27-year experience with splenectomy for Gaucher's disease. Am J Surg. 1991;161(1):69-75.
47. Kyllerman M, Conradi N, Mansson JE, Percy AK, Svennerholm L. Rapidly progressive type III Gaucher disease: deterioration following partial splenectomy. Acta Paediatr Scand. 1990;79(4): 448-453.
48. Mistry P, Sirrs S, Chan A, et al. Pulmonary hypertension in type 1 Gaucher's disease: genetic and epigenetic determinants of phenotype and response to therapy. Mol Genet Metab. 2002;77(1-2):91.
49. Blom S, Erikson A. Gaucher disease: Norrbottnian type; neurodevelopmental, neurological, and neurophysiological aspects. Eur J Pediatr. 1983;140(4):316-322.
50. Kauli R, Zaizov R, Lazar L, et al. Delayed growth and puberty in patients with Gaucher disease type 1: natural history and effect of splenectomy and/or enzyme replacement therapy. Isr Med Assoc J. 2000;2(2):158-163.
51. Kaplan P, Mazur A, Manor O, et al. Acceleration of retarded growth in children with Gaucher disease after treatment with alglucerase. J Pediatr. 1996;129(1):149-153.
52. Zimran A, Morris E, Mengel E, et al. The female Gaucher patient: the impact of enzyme replacement therapy around key reproductive events (menstruation, pregnancy and menopause). Blood Cells Mol Dis. 2009;43(3):264-288.
53. Rosenbloom B, Balwani M, Bronstein JM, et al. The incidence of parkinsonism in patients with type 1 Gaucher disease: data from the ICGG Gaucher Registry. Blood Cells Mol Dis. 2011;46(1):95-102.
54. Westbroek W, Gustafson AM, Sidransky E. Exploring the link between glucocerebrosidase mutations and parkinsonism. Trends Mol Med. 2011;17(9):485-493.
55. Cullen V, Sardi SP, Ng J, et al. Acid beta-glucosidase mutants linked to Gaucher disease, Parkinson disease, and Lewy body dementia alter t-synuclein processing. Ann Neurol. 2011;69(6):940-953.
56. Sardi SP, Clarke J, Kinnecom C, et al. CNS expression of glucocerebrosidase corrects {alpha}-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy. Proc Natl Acad Sci U S A. 2011;108(29):12101-12106.
57. Mazzulli JR, Xu YH, Sun Y, et al. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011;146(1):37-52.
58. Gupta N, Oppenheim IM, Kauvar EF, Tayebi N, Sidransky E. Type 2 Gaucher disease: phenotypic variation and genotypic heterogeneity. Blood Cells Mol Dis. 2011;46(1):75-84.
59. Mignot C, Doummar D, Maire I, De Villemeur TB. Type 2 Gaucher disease: 15 new cases and review of the literature. Brain Dev. 2006;28(1):39-48.
60. Cindik N, Ozcay F, Suren D, et al. Gaucher disease with communicating hydrocephalus and cardiac involvement. Clin Cardiol. 2010;33(1): E26-E30.
61. Uyama E, Takahashi K, Owada M, et al. Hydrocephalus, corneal opacities, deafness, valvular heart disease, deformed toes and leptomeningeal fibrous thickening in adult siblings: a new syndrome associated with beta-glucocerebrosidase deficiency and a mosaic population of storage cells. Acta Neurol Scand. 1992;86(4):407-420.
62. Uyama E, Uchino M, Ida H, Eto Y, Owada M. D409H/D409H genotype in Gaucher-like disease. J Med Genet. 1997;34(2):175.
63. George R, McMahon J, Lytle B, Clark B, Lichtin A. Severe valvular and aortic arch calcification in a patient with Gaucher's disease homozygous for the D409H mutation. Clin Genet. 2001;59(5):360-363.
64. Aksu T, Baysal E, Biyikoglu F, Tufekcioglu O. Gaucher's disease with valvular, myocardial and aortic involvement in a patient with oculomotor apraxia. Anadolu Kardiyol Derg. 2011;11(1):E4-E5.
65. Erduran E, Mocan H, Gedik Y, Kamaci R, Okten A, Deger O. Hydrocephalus, corneal opacities, deafness, left ventricle hypertrophy, clinodactyly in an adolescent patient: a new syndrome associated with glucocerebrosidase deficiency. Genet Couns. 1995;6(3):211-215.
66. Zimran A, Kay A, Gelbart T, et al. Gaucher disease. Clinical, laboratory, radiologic, and genetic features of 53 patients. Medicine (Baltimore). 1992;71(6):337-353.
67. Weinreb NJ, Deegan P, Kacena KA, et al. Life expectancy in Gaucher disease type 1. Am J Hematol. 2008;83(12):896-900.
68. Rosenbloom BE, Weinreb NJ, Zimran A, Kacena KA, Charrow J, Ward E. Gaucher disease and cancer incidence: a study from the Gaucher Registry. Blood. 2005;105(12):4569-4572.
69. De Fost M, Vom Dahl S, Weverling GJ, et al. Increased incidence of cancer in adult Gaucher disease in Western Europe. Blood Cells Mol Dis. 2006;36(1):53-58.
70. Deegan PB, Moran MT, McFarlane I, et al. Clinical evaluation of chemokine and enzymatic biomarkers of Gaucher disease. Blood Cells Mol Dis. 2005;35(2):259-267.
71. Bracoud L, Ahmad H, Brill-Almon E, Chertkoff R. Improving the accuracy of MRI spleen and liver volume measurements: a phase III Gaucher disease clinical trial setting as a model. Blood Cells Mol Dis. 2011;46(1):47-52.
72. Maas M, Poll LW, Terk MR. Imaging and quantifying skeletal involvement in Gaucher disease. Br J Radiol. 2002;75 Suppl 1:A13-A24.
73. Bembi B, Ciana G, Mengel E, Terk MR, Martini C, Wenstrup RJ. Bone complications in children with Gaucher disease. Br J Radiol. 2002; 75 Suppl 1:A37-A44.
74. Ciana G, Addobbati R, Tamaro G, et al. Gaucher disease and bone: laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy. J Inherit Metab Dis. 2005;28(5):723-732.
75. Andersson H, Kaplan P, Kacena K, Yee J. Eight-year clinical outcomes of long-term enzyme replacement therapy for 884 children with Gaucher disease type 1. Pediatrics. 2008;122(6):1182-1190.
76. Sims KB, Pastores GM, Weinreb NJ, et al. Improvement of bone disease by imiglucerase (Cerezyme) therapy in patients with skeletal manifestations of type 1 Gaucher disease: results of a 48-month longitudinal cohort study. Clin Genet. 2008;73(5):430-440.
77. Damiano AM, Pastores GM, Ware JE Jr. The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study. Qual Life Res. 1998;7(5): 373-386.
78. Hayes RP, Grinzaid KA, Duffey EB, Elsas LJ 2nd. The impact of Gaucher disease and its treatment on quality of life. Qual Life Res. 1998;7(6):521-534.
79. Weinreb N, Barranger J, Packman S, et al. Imiglucerase (Cerezyme) improves quality of life in patients with skeletal manifestations of Gaucher disease. Clin Genet. 2007;71(6):576-588.
80. Wraith JE, Clarke LA, Beck M, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004;144(5):581-588.
81. Muenzer J, Wraith JE, Beck M, et al. A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome). Genet Med. 2006;8(8):465-473.
82. Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: a phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr. 2006;148(4):533-539.
83. MacDermot KD, Holmes A, Miners AH. Anderson-Fabry disease: clinical manifestations and impact of disease in a cohort of 98 hemizygous males. J Med Genet. 2001;38(11):750-760.
84. Eng CM, Guffon N, Wilcox WR, et al. Safety and efficacy of recombinant human alpha-galactosidase A: replacement therapy in Fabry's disease. N Engl J Med. 2001;345(1):9-16.
85. Germain DP, Waldek S, Banikazemi M, et al. Sustained, long-term renal stabilization after 54 months of agalsidase beta therapy in patients with Fabry disease. J Am Soc Nephrol. 2007;18(5):1547-1557.
86. Brady RO, Kanfer JN, Bradley RM, Shapiro D. Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher's disease. J Clin Invest. 1966;45(7):1112-1115.
87. Weinreb NJ, Brady RO, Tappel AL. The lysosomal localization of sphingolipid hydrolases. Biochim Biophys Acta. 1968;159(1):141-146.
88. De Duve C. The lysosome. Sci Am. 1963;208:64-72.
89. Appelmans F, Wattiaux R, de Duve C. Tissue fractionation studies: 5. The association of acid phosphatase with a special class of cytoplasmic granules in rat liver. Biochem J. 1955;59(3):438-445.
90. Fratantoni JC, Hall CW, Neufeld EF. Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts. Science. 1968;162(853):570-572.
91. Hickman S, Shapiro LJ, Neufeld EF. A recognition marker required for uptake of a lysosomal enzyme by cultured fibroblasts. Biochem Biophys Res Commun. 1974;57(1):55-61.
92. Kaplan A, Achord DT, Sly WS. Phosphohexosyl components of a lysosomal enzyme are recognized by pinocytosis receptors on human fibroblasts. Proc Natl Acad Sci U S A. 1977;74(5): 2026-2030.
93. Sando GN, Neufeld EF. Recognition and receptor-mediated uptake of a lysosomal enzyme, alpha-l-iduronidase, by cultured human fibroblasts. Cell. 1977;12(3):619-627.
94. Kornfeld S. A fascination with sugars. Mol Biol Cell. 2010;21(22): 3773-3775.
95. Hasilik A, Waheed A, Cantz M, von Figura K. Oligosaccharides in lysosomal enzymes. Distribution of high-mannose and complex oligosaccharides in cathepsin D and beta-hexosaminidase. Eur J Biochem. 1982;122(1):119-123.
96. Aerts JM, Schram AW, Strijland A, et al. Glucocerebrosidase, a lysosomal enzyme that does not undergo oligosaccharide phosphorylation. Biochim Biophys Acta. 1988;964(3):303-308.
97. Brady RO, Pentchev PG, Gal AE, Hibbert SR, Dekaban AS. Replacement therapy for inherited enzyme deficiency. Use of purified glucocerebrosidase in Gaucher's disease. N Engl J Med. 1974;291(19): 989-993.
98. Furbish FS, Blair HE, Shiloach J, Pentchev PG, Brady RO. Enzyme replacement therapy in Gaucher's disease: large-scale purification of glucocerebrosidase suitable for human administration. Proc Natl Acad Sci U S A. 1977;74(8):3560-3563.
99. Dale GL, Beutler E. Enzyme replacement therapy in Gaucher's disease: a rapid, high-yield method for purification of glucocerebrosidase. Proc Natl Acad Sci U S A. 1976;73(12):4672-4674.
100. Dale GL, Villacorte DG, Beutler E. Solubilization of glucocerebrosidase from human placenta and demonstration of a phospholipid requirement for its catalytic activity. Biochem Biophys Res Commun. 1976;71(4):1048-1053.
101. Brady RO, Pentchev PG, Gal AE, et al. Enzyme replacement therapy for the sphingolipidoses. Adv Exp Med Biol. 1976;68: 523-532.
102. Furbish FS, Steer CJ, Barranger JA, Jones EA, Brady RO. The uptake of native and desialylated glucocerebrosidase by rat hepatocytes and Kupffer cells. Biochem Biophys Res Commun. 1978;81(3): 1047-1053.
103. Brady RO. Enzyme replacement in the sphingolipidoses. In: Barranger J, Brady RO, editors. Molecular Basis of Lysosomal Storage Disorders. Vol 1. Orlando (FL): Academic Press; 1984:461-478.
104. Morrone S, Pentchev PG, Baynes J, Thorpe S. Studies in vivo of the tissue uptake, cellular distribution and catabolic turnover of exogenous glucocerebrosidase in rat. Biochem J. 1981;194(3): 733-742.
105. Beutler E, Dale GL, Guinto DE, Kuhl W. Enzyme replacement therapy in Gaucher's disease: preliminary clinical trial of a new enzyme preparation. Proc Natl Acad Sci U S A. 1977;74(10):4620-4623.
106. Dale GL, Kuhl W, Beutler E. Incorporation of glucocerebrosidase into Gaucher's disease monocytes in vitro. Proc Natl Acad Sci U S A. 1979;76(1):473-475.
107. Hudgin RL, Pricer WE Jr, Ashwell G, Stockert RJ, Morell AG. The isolation and properties of a rabbit liver binding protein specific for asialoglycoproteins. J Biol Chem. 1974;249(17):5536-5543.
108. Neufeld EF. From serendipity to therapy. Annu Rev Biochem. 2011; 80:1-15.
109. Stahl PD, Rodman JS, Miller MJ, Schlesinger PH. Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages. Proc Natl Acad Sci U S A. 1978;75(3):1399-1403.
110. Robbins JC, Lam MH, Tripp CS, Bugianesi RL, Ponpipom MM, Shen TY. Synthetic glycopeptide substrates for receptor-mediated endocytosis by macrophages. Proc Natl Acad Sci U S A. 1981;78(12): 7294-7298.
111. Achord DT, Brot FE, Bell CE, Sly WS. Human beta-glucuronidase: in vivo clearance and in vitro uptake by a glycoprotein recognition system on reticuloendothelial cells. Cell. 1978;15(1):269-278.
112. Takasaki S, Murray GJ, Furbish FS, Brady RO, Barranger JA, Kobata A. Structure of the N-asparagine-linked oligosaccharide units of human placental beta-glucocerebrosidase. J Biol Chem. 1984;259(16):10112-10117.
113. Furbish FS, Oliver KL, Zirzow GC, Brady RO, Barranger JA. Interaction of human placental glucocerebrosidase with hepatic lectins. In: Barranger JA, Brady RO, editors. The Molecular Basis of Lysosomal Storage Disorders. Orlando (FL): Academic Press; 1984:219-232.
114. Pricer WE Jr, Hudgin RL, Ashwell G, Stockert RJ, Morell AG. A membrane receptor protein for asialoglycoproteins. Methods Enzymol. 1974;34:688-691.
115. Furbish FS, Steer CJ, Krett NL, Barranger JA. Uptake and distribution of placental glucocerebrosidase in rat hepatic cells and effects of sequential deglycosylation. Biochim Biophys Acta. 1981;673(4):425-434.
116. Doebber TW, Wu MS, Bugianesi RL, et al. Enhanced macrophage uptake of synthetically glycosylated human placental beta-glucocerebrosidase. J Biol Chem. 1982;257(5):2193-2199.
117. Murray GJ. Lectin-specific targeting of lysosomal enzymes to reticuloendothelial cells. Methods Enzymol. 1987;149:25-42.
118. Natowicz MR, Chi MM, Lowry OH, Sly WS. Enzymatic identification of mannose 6-phosphate on the recognition marker for receptormediated pinocytosis of beta-glucuronidase by human fibroblasts. Proc Natl Acad Sci U S A. 1979;76(9):4322-4326.
119. Parker RI, Barton NW, Read EJ, Brady RO. Hematologic improvement in a patient with Gaucher disease on long-term enzyme replacement therapy: evidence for decreased splenic sequestration and improved red blood cell survival. Am J Hematol. 1991;38(2):130-137.
120. Murray GJ, Howard KD, Richards SM, Barton NW, Brady RO. Gaucher's disease: lack of antibody response in 12 patients following repeated intravenous infusions of mannose terminal glucocerebrosidase. J Immunol Methods. 1991;137(1):113-120.
121. Richards SM, Olson TA, McPherson JM. Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. Blood. 1993;82(5):1402-1409.
122. Beutler E, Kay A, Saven A, et al. Enzyme replacement therapy for Gaucher disease. Blood. 1991;78(5):1183-1189.
123. Fallet S, Grace ME, Sibille A, et al. Enzyme augmentation in moderate to life-threatening Gaucher disease. Pediatr Res. 1992;31(5): 496-502.
124. Mistry PK, Davies S, Corfield A, Dixon AK, Cox TM. Successful treatment of bone marrow failure in Gaucher's disease with low-dose modified glucocerebrosidase. Q J Med. 1992;83(303): 541-546.
125. Grabowski GA, Barton NW, Pastores G, et al. Enzyme therapy in type 1 Gaucher disease: comparative efficacy of mannose-terminated glucocerebrosidase from natural and recombinant sources. Ann Intern Med. 1995;122(1):33-39.
126. Mistry PK, Wraight EP, Cox TM. Therapeutic delivery of proteins to macrophages: implications for treatment of Gaucher's disease. Lancet. 1996;348(9041):1555-1559.
127. Friedman B, Vaddi K, Preston C, Mahon E, Cataldo JR, McPherson JM. A comparison of the pharmacological properties of carbohydrate remodeled recombinant and placental-derived beta-glucocerebrosidase: implications for clinical efficacy in treatment of Gaucher disease. Blood. 1999;93(9):2807-2816.
128. Hollak CE, Aerts JM, Goudsmit R, et al. Individualised low-dose alglucerase therapy for type 1 Gaucher's disease. Lancet. 1995;345(8963): 1474-1478.
129. Figueroa ML, Rosenbloom BE, Kay AC, et al. A less costly regimen of alglucerase to treat Gaucher's disease. N Engl J Med. 1992;327(23): 1632-1636.
130. Mistry PK, Weinreb NJ, Brady RO, Grabowski GA. Gaucher disease: resetting the clinical and scientific agenda. Am J Hematol. 2009;84(4): 205-207.
131. Zimran A, Ilan Y, Elstein D. Enzyme replacement therapy for mild patients with Gaucher disease. Am J Hematol. 2009;84(4):202-204.
132. Hollak CE, van Weely S, van Oers MH, Aerts JM. Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest. 1994;93(3):1288-1292.
133. Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(4 Suppl 5):4-14.
134. Weinreb N, Taylor J, Cox T, Yee J, vom Dahl S. A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase. Am J Hematol. 2008;83(12):890-895.
135. Grabowski GA, Kacena K, Cole JA, et al. Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1. Genet Med. 2009;11(2): 92-100.
136. Goldman DP, Clarke AE, Garber AM. Creating the costliest orphan: the Orphan Drug Act in the development of Ceredase. Int J Technol Assess Health Care. 1992;8(4):583-597.
137. Connock M, Burls A, Frew E, et al. The clinical effectiveness and cost-effectiveness of enzyme replacement therapy for Gaucher's disease: a systematic review. Health Technol Assess. 2006;10(24):iii-iv, ix-136.
138. Meeker D, Termeer HA. Meeting the needs of patients with Gaucher disease: pioneering a sustainable model for ultra-orphan diseases. In: Futerman AH, Zimran A, editors. Gaucher Disease. Vol 1. Boca Raton (FL): CRC Press; 2007:465-472.
139. Charrow J, Dulisse B, Grabowski GA, Weinreb NJ. The effect of enzyme replacement therapy on bone crisis and bone pain in patients with type 1 Gaucher disease. Clin Genet. 2007;71(3):205-211.
140. Starzyk K, Richards S, Yee J, Smith SE, Kingma W. The long-term international safety experience of imiglucerase therapy for Gaucher disease. Mol Genet Metab. 2007;90(2):157-163.
141. Cox TM, Aerts JM, Belmatoug N, et al. Management of nonneuronopathic Gaucher disease with special reference to pregnancy, splenectomy, bisphosphonate therapy, use of biomarkers and bone disease monitoring. J Inherit Metab Dis. 2008;31(3):319-336.
142. Wenstrup RJ, Bailey L, Grabowski GA, et al. Gaucher disease: alendronate disodium improves bone mineral density in adults receiving enzyme therapy. Blood. 2004;104(5):1253-1257.
143. Lebel E, Dweck A, Foldes AJ, et al. Bone density changes with enzyme therapy for Gaucher disease. J Bone Miner Metab. 2004;22(6): 597-601.
144. Rudzki Z, Okon K, Machaczka M, Rucinska M, Papla B, Skotnicki AB. Enzyme replacement therapy reduces Gaucher cell burden but may accelerate osteopenia in patients with type I disease: a histological study. Eur J Haematol. 2003;70(5):273-281.
145. Marini JC. Do bisphosphonates make children's bones better or brittle? N Engl J Med. 2003;349(5):423-426.
146. Bembi B, Agosti E, Boehm P, Nassimbeni G, Zanatta M, Vidoni L. Aminohydroxypropylidene-biphosphonate in the treatment of bone lesions in a case of Gaucher's disease type 3. Acta Paediatr. 1994;83(1): 122-124.
147. Ostlere L, Warner T, Meunier PJ, et al. Treatment of type 1 Gaucher's disease affecting bone with aminohydroxypropylidene bisphosphonate (pamidronate). Q J Med. 1991;79(290):503-515.
148. Rosenbaum H, Sidransky E. Cholelithiasis in patients with Gaucher disease. Blood Cells Mol Dis. 2002;28(1):21-27.
149. Taddei TH, Dziura J, Chen S, et al. High incidence of cholesterol gallstone disease in type 1 Gaucher disease: characterizing the biliary phenotype of type 1 Gaucher disease. J Inherit Metab Dis. 2010;33(3): 291-300.
150. Lo SM, Liu J, Chen F, et al. Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long-term outcomes of therapy. J Inherit Metab Dis. 2011;34(3):643-650.
151. Cox T, Lachmann R, Hollak C, et al. Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis. Lancet. 2000;355(9214):1481-1485.
152. Elstein D, Hollak C, Aerts JM, et al. Sustained therapeutic effects of oral miglustat (Zavesca, N-butyldeoxynojirimycin, OGT 918) in type I Gaucher disease. J Inherit Metab Dis. 2004;27(6):757-766.
153. Cox TM, Aerts JM, Andria G, et al. The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: a position statement. J Inherit Metab Dis. 2003;26(6):513-526.
154. Brumshtein B, Salinas P, Peterson B, et al. Characterization of geneactivated human acid-beta-glucosidase: crystal structure, glycan composition, and internalization into macrophages. Glycobiology. 2010;20(1):24-32.
155. Van Patten SM, Hughes H, Huff MR, et al. Effect of mannose chain length on targeting of glucocerebrosidase for enzyme replacement therapy of Gaucher disease. Glycobiology. 2007;17(5):467-478.
156. Zimran A, Altarescu G, Philips M, et al. Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. 2010;115(23): 4651-4656.
157. Elstein D, Cohn GM, Wang N, Djordjevic M, Brutaru C, Zimran A. Early achievement and maintenance of the therapeutic goals using velaglucerase alfa in type 1 Gaucher disease. Blood Cells Mol Dis. 2011;46(1):119-123.
158. Elstein D, Foldes AJ, Zahrieh D, et al. Significant and continuous improvement in bone mineral density among type 1 Gaucher disease patients treated with velaglucerase alfa: 69-month experience, including dose reduction. Blood Cells Mol Dis. 2011;47(1):56-61.
159. Shaaltiel Y, Bartfeld D, Hashmueli S, et al. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. Plant Biotechnol J. 2007;5(5):579-590.
160. Aviezer D, Brill-Almon E, Shaaltiel Y, et al. A plant-derived recombinant human glucocerebrosidase enzyme: a preclinical and phase I investigation. PLoS One. 2009;4(3):e4792.
161. Zimran A, Brill-Almon E, Chertkoff R, et al. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011;118(22):5767-5773.
162. Inokuchi J, Radin NS. Preparation of the active isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibitor of murine glucocerebroside synthetase. J Lipid Res. 1987;28(5):565-571.
163. Abe A, Radin NS, Shayman JA, et al. Structural and stereochemical studies of potent inhibitors of glucosylceramide synthase and tumor cell growth. J Lipid Res. 1995;36(3):611-621.
164. McEachern KA, Fung J, Komarnitsky S, et al. A specific and potent inhibitor of glucosylceramide synthase for substrate inhibition therapy of Gaucher disease. Mol Genet Metab. 2007;91(3):259-267.
165. Lee L, Abe A, Shayman JA. Improved inhibitors of glucosylceramide synthase. J Biol Chem. 1999;274(21):14662-14669.
166. Cox TM. Eliglustat tartrate, an orally active glucocerebroside synthase inhibitor for the potential treatment of Gaucher disease and other lysosomal storage diseases. Curr Opin Investig Drugs. 2010;11(10):1169-1181.
167. Peterschmitt MJ, Burke A, Blankstein L, et al. Safety, tolerability, and pharmacokinetics of eliglustat tartrate (Genz-112638) after single doses, multiple doses, and food in healthy volunteers. J Clin Pharmacol. 2011;51(5):695-705.
168. Lukina E, Watman N, Arreguin EA, et al. Improvement in hematological, visceral, and skeletal manifestations of Gaucher disease type 1 with oral eliglustat tartrate (Genz-112638) treatment: 2-year results of a phase 2 study. Blood. 2010;116(20):4095-4098.
169. Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1028 patients with type 1 Gaucher disease after 2 to 5 years of treatment: a report from the Gaucher Registry. Am J Med. 2002;113(2):112-119.
170. Roos JC, Hyry HI, Cox TM. Orphan drug pricing may warrant a competition law investigation. BMJ. 2010;341:c6471.
171. Hollak CE, vom Dahl S, Aerts JM, et al. Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis. 2010;44(1): 41-47.
172. Walsh G. Biopharmaceutical benchmarks 2010. Nat Biotechnol. 2010;28(9):917-924.