Gaucher Disease Medication

  • Author: Ellen Sidransky, MD; Chief Editor: Bruce Buehler, MD   more...
 
Updated: May 4, 2012
 

Medication Summary

Several therapies have been approved by the US Food and Drug Administration (FDA) for the treatment of type 1 Gaucher disease. Enzyme replacement therapy (ERT) with glucocerebrosidase purified from human placenta was FDA approved in 1991, followed by approval in 1994 of a recombinant form of the enzyme produced in cultured Chinese hamster ovary (CHO) cells, marketed as imiglucerase (Cerezyme). Worldwide, over 4,000 patients with Gaucher disease have received ERT, which is safe and well tolerated.

In 2010, an alternate form of ERT was approved. This form of recombinant enzyme is produced in cultured human cells and is marketed as velaglucerase alfa (VPRIV).[4, 5] In May 2012, taliglucerase alfa (Elelyso) was the first plant cell–based ERT approved by the FDA; it uses engineered carrot cells.

Approximately 10-15% of patients with Gaucher disease treated with imiglucerase develop antibodies to the enzyme protein, but few develop any significant allergic reactions, which are controlled with premedication with hydrocortisone, antihistamines, or both. All antibodies have immunoglobulin G (IgG), mostly of the IgG1 subclass. A few patients with Gaucher disease have developed antibodies that impair enzyme activity. No antibody production has been reported with velaglucerase alfa.

Oral substrate reduction therapy, using an aminosugar inhibitor of glucosylceramide synthase, has been approved for use in patients with type 1 Gaucher disease in whom ERT is not a therapeutic option because of allergy, hypersensitivity, or poor venous access. Although oral substrate reduction therapy was approved by the FDA in 2003, long-term data regarding efficacy and safety are not yet available.

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Enzyme replacement therapy

Class Summary

In most cases, ERT is highly effective in reversing the visceral and hematologic manifestations of type 1 Gaucher disease. Recombinant beta-glucocerebrosidase (imiglucerase [Cerezyme]) has replaced the original tissue-derived product, alglucerase (Ceredase). Alglucerase is an orphan drug and still manufactured by Genzyme Corporation on an extremely limited basis for a few patients unable to tolerate the newer recombinant product. Presymptomatic use is controversial because of the high cost and the extremely variable clinical course.

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Imiglucerase (Cerezyme)

 

A recombinant-derived analog of beta-glucocerebrosidase produced in mammalian cell culture and chemically modified by mannose termination of glycosylated amino acids. Catalyzes hydrolytic cleavage of glucocerebroside (a glycoprotein) to glucose and ceramide within the lysosomes of phagocytic cells in the reticuloendothelial system. Treatment with recombinant enzyme improves anemia and thrombocytopenia, reduces spleen and liver size, and decreases cachexia

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Velaglucerase alfa (VPRIV)

 

Hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy for type 1 Gaucher disease. Improves symptoms associated with the disease, including anemia, thrombocytopenia, increased spleen and liver size, and cachexia.

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Taliglucerase alfa (Elelyso)

 

Taliglucerase is a plant-based recombinant enzyme. It catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, which results in reduced spleen and liver enlargement and increased RBCs and platelets.

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Glucosylceramide synthase inhibitors:

Class Summary

These agents inhibit the enzyme glucosylceramide synthase, the initial enzyme in a series of reactions that result in the synthesis of most glycosphingolipids, including glucocerebroside. The goal of treatment is to reduce the rate of glucocerebroside biosynthesis so that the amount is reduced to a level that allows the residual activity of the deficient glucocerebrosidase enzyme to be more effective (substrate reduction therapy).

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Miglustat (Zavesca)

 

Indicated for type 1 Gaucher disease in patients in whom ERT is not a therapeutic option. Reduces GSL production by inhibiting glucosylceramide synthase. Reduces spleen and liver volume and increases hemoglobin and platelet counts.

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Contributor Information and Disclosures
Author

Ellen Sidransky, MD  Senior Investigator, Chief, Section on Molecular Neurogenetics, Medical Genetics Branch, National Human Genome Research Institute, NIH

Ellen Sidransky, MD is a member of the following medical societies: American Society of Human Genetics, Movement Disorders Society, Society for Inherited Metabolic Disorders, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Robert D Steiner, MD  Credit Unions for Kids Professor of Pediatric Research, Professor of Pediatrics and Molecular and Medical Genetics, Vice Chair for Research, Department of Pediatrics, Faculty, Program in Molecular and Cellular Biosciences, Oregon Health and Science University School of Medicine; Attending Physician, Doernbecher Children's Hospital; Staff Consultant, Director of Metabolic Bone Disease Clinic, Shriners Hospital Portland

Robert D Steiner, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American College of Medical Genetics, American Society of Human Genetics, Oregon Medical Association, Society for Inherited Metabolic Disorders, Society for Pediatric Research, Society for the Study of Inborn Errors of Metabolism, and Western Society for Pediatric Research

Disclosure: Amicus Honoraria Consulting; Actelion Honoraria Consulting; Actelion Honoraria Speaking and teaching; Biomarin Honoraria Consulting; Genzyme Honoraria Consulting; Shire Honoraria Consulting

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

References

  1. Grabowski GA. Phenotype, diagnosis, and treatment of Gaucher's disease. Lancet. Oct 4 2008;372(9645):1263-71. [Medline].

  2. [Best Evidence] Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER. Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease. N Engl J Med. Oct 22 2009;361(17):1651-61. [Medline].

  3. Sidransky E, Pastores GM, Mori M. Dosing enzyme replacement therapy for Gaucher disease: older, but are we wiser?. Genet Med. Feb 2009;11(2):90-1. [Medline].

  4. Zimran A, Altarescu G, Phillips M, Attias D, Jmoudiak M, Deeb M. Phase I/II and extension study of velaglucerase alfa (Gene-ActivatedTM human glucocerebrosidase) replacement therapy in adults with type 1 Gaucher disease: 48-month experience. Blood. Mar 18 2010;[Medline].

  5. Sidransky E, Pastores GM, Mori M. Dosing enzyme replacement therapy for Gaucher disease: older, but are we wiser?. Genet Med. Feb 2009;11(2):90-1. [Medline].

  6. 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. Dec 2008;122(6):1182-90. [Medline].

  7. Mitsui J, Mizuta I, Toyoda A, Ashida R, et al. Mutations for Gaucher disease confer high susceptibility to Parkinson disease. Arch Neurol. May 2009;66(5):571-6. [Medline].

  8. Weinreb NJ, Deegan P, Kacena KA, Mistry P, Pastores GM, Velentgas P, et al. Life expectancy in Gaucher disease type 1. Am J Hematol. Dec 2008;83(12):896-900. [Medline].

  9. Mamopoulos AM, Hughes DA, Tuck SM, Mehta AB. Gaucher disease and pregnancy. J Obstet Gynaecol. Apr 2009;29(3):240-2. [Medline].

  10. Amato D, Stachiw T, Clarke JT, Rivard GE. Gaucher disease: variability in phenotype among siblings. J Inherit Metab Dis. 2004;27(5):659-69. [Medline].

  11. Andersson HC, Charrow J, Kaplan P, et al. Individualization of long-term enzyme replacement therapy for Gaucher disease. Genet Med. Feb 2005;7(2):105-10. [Medline].

  12. 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. May 23 1991;324(21):1464-70. [Medline].

  13. Beutler E. Lysosomal storage diseases: natural history and ethical and economic aspects. Mol Genet Metab. Jul 2006;88(3):208-15. [Medline].

  14. Beutler E, Gelbart T, Scott CR. Hematologically important mutations: Gaucher disease. Blood Cells Mol Dis. Nov-Dec 2005;35(3):355-64. [Medline].

  15. Beutler E, Grabowski GA, CR Scriver, et al Eds. The Metabolic and Molecular Bases of Inherited Disease. McGraw-Hill, New York. 2001;3635-68.

  16. Bohlega S, Kambouris M, Shahid M, et al. Gaucher disease with oculomotor apraxia and cardiovascular calcification (Gaucher type IIIC). Neurology. Jan 11 2000;54(1):261-3. [Medline].

  17. Charrow J, Andersson HC, Kaplan P, et al. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. Jan 2004;144(1):112-20. [Medline].

  18. 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):513-26. [Medline].

  19. Depaolo J, Goker-Alpan O, Samaddar T, Lopez G, Sidransky E. The association between mutations in the lysosomal protein glucocerebrosidase and parkinsonism. Mov Disord. May 7 2009;[Medline].

  20. Futerman AH, Zimran A. Gaucher Disease. CRC Press, Boca Raton, FL. 2006.

  21. Goker-Alpan O, Schiffmann R, Park JK, et al. Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediatr. Aug 2003;143(2):273-6. [Medline].

  22. 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. Feb 2009;11(2):92-100. [Medline].

  23. Grabowski GA, Leslie N, Wenstrup R. Enzyme therapy for Gaucher disease: the first 5 years. Blood Rev. Jun 1998;12(2):115-33. [Medline].

  24. Itzchaki M, Lebel E, Dweck A, et al. Orthopedic considerations in Gaucher disease since the advent of enzyme replacement therapy. Acta Orthop Scand. Dec 2004;75(6):641-53. [Medline].

  25. Jmoudiak M, Futerman AH. Gaucher disease: pathological mechanisms and modern management. Br J Haematol. Apr 2005;129(2):178-88. [Medline].

  26. 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. Jun 2000;66(6):1777-86. [Medline]. [Full Text].

  27. [Guideline] Langlois S, Wilson RD. Carrier screening for genetic disorders in individuals of Ashkenazi Jewish descent. J Obstet Gynaecol Can. Apr 2006;28(4):324-43. [Medline].

  28. Lwin A, Orvisky E, Goker-Alpan O, et al. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab. Jan 2004;81(1):70-3. [Medline].

  29. Mistry PK, Abrahamov A. A practical approach to diagnosis and management of Gaucher's disease. Baillieres Clin Haematol. Dec 1997;10(4):817-38. [Medline].

  30. NIH Technology Assessment Panel on Gaucher Disease. Gaucher disease. Current issues in diagnosis and treatment. JAMA. Feb 21 1996;275(7):548-53. [Medline].

  31. Park JK, Orvisky E, Tayebi N, et al. Myoclonic epilepsy in Gaucher disease: genotype-phenotype insights from a rare patient subgroup. Pediatr Res. Mar 2003;53(3):387-95. [Medline].

  32. Sibille A, Eng CM, Kim SJ, et al. Phenotype/genotype correlations in Gaucher disease type I: clinical and therapeutic implications. Am J Hum Genet. Jun 1993;52(6):1094-101. [Medline]. [Full Text].

  33. Sidransky E. Gaucher disease: complexity in a "simple" disorder. Mol Genet Metab. Sep-Oct 2004;83(1-2):6-15. [Medline].

  34. Svennerholm L, Erikson A, Groth CG, et al. Norrbottnian type of Gaucher disease--clinical, biochemical and molecular biology aspects: successful treatment with bone marrow transplantation. Dev Neurosci. 1991;13(4-5):345-51. [Medline].

  35. Tayebi N, Stone DL, Sidransky E. Type 2 gaucher disease: an expanding phenotype. Mol Genet Metab. Oct 1999;68(2):209-19. [Medline].

  36. Tayebi N, Stubblefield BK, Park JK, et al. Reciprocal and nonreciprocal recombination at the glucocerebrosidase gene region: implications for complexity in Gaucher disease. Am J Hum Genet. Mar 2003;72(3):519-34. [Medline].

  37. Weinreb NJ, Aggio MC, Andersson HC, et al. Gaucher disease type 1: revised recommendations on evaluations and monitoring for adult patients. Semin Hematol. Oct 2004;41(4 Suppl 5):15-22. [Medline].

  38. Wenstrup RJ, Roca-Espiau M, Weinreb NJ, Bembi B. Skeletal aspects of Gaucher disease: a review. Br J Radiol. 2002;75 Suppl 1:A2-12. [Medline]. [Full Text].

  39. Zimran A, Altarescu G, Rudensky B, et al. Survey of hematological aspects of Gaucher disease. Hematology. Apr 2005;10(2):151-6. [Medline].

 
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