Abstract
The introduction of enzyme supplementation therapy for Gaucherdisease has had a great impact on the lives of many patients. Organomegaly, cytopenia and bone disease have been shown to improve in response to treatment, resulting in an improvement in quality of life. However, the assessment of organ system involvement is not always done in such a way that the relationship with clinically relevant endpoints is clear. The lack of adequately validated methods of assessment, especially for bone disease, has hindered the establishment of treatment goals and guidelines for treatment optimization.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
Aerts JM, Hollak CE (1997) Plasma and metabolic abnormalities in Gaucher's disease. Baillieres Clin Haematol 10: 691–709.
Barton NW, Brady RO, Dambrosia JM, et al (1991) Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebrosidase for Gaucher's disease. N Engl J Med 324: 1464–1470.
Beutler E, Demina A, Laubscher K, et al (1995) The clinical course of treated and untreated Gaucher disease. A study of 45 patients. Blood Cells Mol Dis 21: 86–108.
Beutler E, Grabowski G (1995) Gaucher disease. In Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Basis of Inherited Disease, 7th edn. New York: McGraw-Hill Publishing Company.
Boot RG, Renkema GH, Verhoek M, et al (1998) The human chitotriosidase gene. Nature of inherited enzyme deficiency. J Biol Chem 273: 25680–25685.
Charrow J, Andersson HC, Kaplan P, et al (2000) The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med 160: 2835–2843.
Charrow J, Esplin JA, Gribble TJ, et al (1998) Gaucher disease: recommendations on diagnosis, evaluation, and monitoring. Arch Intern Med 158: 1754–1760.
Colburn WA (2000) Optimizing the use of biomarkers, surrogate endpoints, and clinical endpoints for more efficient drug development. J Clin Pharmacol 40(12 Pt 2): 1419–1427.
Cox TM, Schofield JP (1997) Gaucher's disease: clinical features and natural history. Baillieres Clin Haematol 10: 657–689.
Cummings SR, Black DM, Nevitt MC, et al (1993) Bone density at various sites for prediction of hip fractures. Lancet 341: 72–75.
Damiano AM, Pastores GM, Ware JE Jr (1998) The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study. Qual Life Res 7: 373–386.
Ek M, Guijt M, Oosterveld P, Hollak CEM (1999) Quality of life in patients with Gaucher disease in the Netherlands. Abstract, 3rd Meeting of the European Working Group on Gaucher Disease, Lemnos: 18.
Elstein D, Hadas-Halpern I, Itzchaki M, Lahad A, Abrahamov A, Zimran A (1996) Effect of lowdose ERT on bones in Gaucher disease patients with severe skeletal involvement. Blood Cells Mol Dis 22: 104–111.
Figueroa ML, Rosenbloom BE, Kay AC, et al (1992) A less costly regimen of alglucerase to treat Gaucher's disease. N Engl J Med 327: 1632–1636.
Grabowski GA (1996). Current issues in enzyme therapy for Gaucher disease. Drugs 52: 159–167.
Gielchinsky Y, Elstein D, Hadas-Halpern I, Lahad A, Abrahamov A, Zimran A (1999) Is there a correlation between degree of splenomegaly, symptoms and hypersplenism? A study of 218 patients with Gaucher disease. Br J Haematol 106: 812–816.
Hollak CE, Aerts JM, Goudsmit R, et al (1995) Individualised low-dose alglucerase therapy for type 1 Gaucher's disease. Lancet 345: 1474–1478.
Hollak CE, Corssmit EP, Aerts JM, et al (1997a) Differential effects of enzyme supplementation therapy on manifestations of type 1 Gaucher disease. Am J Med 103: 185–191.
Hollak CE, Levi M, Berends F, Aerts JM, van Oers MH (1997b) Coagulation abnormalities in type 1 Gaucher disease are due to low-grade activation and can be partly restored by enzyme supplementation therapy. Br J Haematol 96: 470–476.
Hollak CE, van Weely S, van Oers MH, Aerts JM (1994) Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease. J Clin Invest 93: 1288–1292.
Johnson LA, Hoppel BE, Gerard EL, et al (1992) Quantitative chemical shift imaging of vertebral bone marrow in patients with Gaucher disease. Radiology 182: 451–455.
Maas M, Akkerman EM, Hollak CEM, et al (1999) Radiological, biochemical and clinical parameters of skeletal disease in relation to fat fraction determination by QCSI in type 1 Gaucher disease. Abstract, 3rd Meeting of the European Working Group on Gaucher Disease, Lemnos: 40.
Masek BJ, Sims KB, Bove CM, Korson MS, Short P, Norman DK (1999) Quality of life assessment in adults with type 1 Gaucher disease. Qual Life Res 8: 263–268.
Miller SP, Zirzow GC, Doppelt SH, Brady RO, Barton NW (1996). Analysis of the lipids of normal and Gaucher bone marrow. J Lab Clin Med 127: 353–358.
NIH Technology Assessment Panel on Gaucher Disease (1996) Current issues in diagnosis and treatment. JAMA 275: 548–553.
Pastores GM, Sibille AR, Grabowski GA (1993) Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months. Blood 82: 408–416.
Rodrigue SW, Rosenthal DI, Barton NW, Zurakowski D, Mankin HJ (1999) Risk factors for osteonecrosis in patients with type 1 Gaucher's disease. Clin Orthop 362: 201–207.
Rose JS, Grabowski GA, Barnett SH, Desnick RJ (1982) Accelerated skeletal deterioration after splenectomy in Gaucher type 1 disease. AJR Am J Roentgenol 139: 1202–1204.
Rosenthal DI, Doppelt SH, Mankin HJ, et al (1995) Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics 96: 629–637.
Van Weely S, Hollak CE, Maas M, Boot RG, Aerts JM (1999) Determination of plasma chitotriosidase in Gaucher disease: practical implications. Abstract, 3rd Meeting of the European Working Group on Gaucher Disease, Lemnos: 71.
Zimran A, Elstein D, Kannai R, et al (1994). Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype, and clinical features on response to treatment. Am J Med 97: 3–13.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hollak, C.E.M., Maas, M. & Aerts, J.M. Clinically relevant therapeutic endpoints in type I Gaucher disease. J Inherit Metab Dis 24 (Suppl 2), 97–105 (2001). https://doi.org/10.1023/A:1012492429191
Issue Date:
DOI: https://doi.org/10.1023/A:1012492429191