The role of the iminosugar N-butyldeoxynojirimycin (miglustat) in the management of type I (non-neuronopathic) Gaucher disease: A position statement

N-Butyldeoxynojirimycin (NB-DNJ, miglustat 'Zavesca') is an orallyactive iminosugar which inhibits the biosynthesis of macromolecular substrates that accumulate pathologically in glycosphingolipidoses. Clinical trials of NB-DNJ in patients with Gaucher's disease demonstrate the therapeutic potential of such substrate inhibitors in the glycolipid storage disorders. However, macrophage-targetted enzyme replacement using intravenous mannose-terminated human glucocerebrosidase (imiglucerase, Cerezyme) is highly effective in ameliorating many of the manifestations of Gaucher's disease and is a treatment in widespread use. Given that imiglucerase and miglustat are now both licensed for the treatment of Gaucher's disease, there is a need to review their therapeutic status. Here the treatment of type 1 (non-neuronopathic) Gaucher disease is evaluated with particular reference to the emerging role of oral N-butyldeoxynojirimycin (miglustat) as a substrate-reducing agent. This position statement represents the consensus viewpoint of an independent international advisory council to the European Working Group on Gaucher Disease.

[1]  N. Radin,et al.  Preparation of the active isomer of 1-phenyl-2-decanoylamino-3-morpholino-1-propanol, inhibitor of murine glucocerebroside synthetase. , 1987, Journal of lipid research.

[2]  J. Aerts,et al.  Individualised low-dose alglucerase therapy for type 1 Gaucher's disease , 1995, The Lancet.

[3]  J. Dambrosia,et al.  Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher's disease. , 1991, The New England journal of medicine.

[4]  D. Elstein,et al.  Withdrawal of enzyme replacement therapy in Gaucher's disease , 2000, British journal of haematology.

[5]  R. Dwek,et al.  Novel oral treatment of Gaucher's disease with N-butyldeoxynojirimycin (OGT 918) to decrease substrate biosynthesis , 2000, The Lancet.

[6]  G. Grabowski,et al.  Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months. , 1993, Blood.

[7]  T. Cox,et al.  Gaucher's disease: clinical features and natural history. , 1997, Bailliere's clinical haematology.

[8]  C. Hollak,et al.  Plasma and metabolic abnormalities in Gaucher's disease. , 1997, Bailliere's clinical haematology.

[9]  R. Dwek,et al.  N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. , 1994, The Journal of biological chemistry.

[10]  R. Schiffmann,et al.  Enzyme Therapy in Type 1 Gaucher Disease: Comparative Efficacy of Mannose-Terminated Glucocerebrosidase from Natural and Recombinant Sources , 1995, Annals of Internal Medicine.

[11]  L. Resnick,et al.  The safety and efficacy of combination N-butyl-deoxynojirimycin (SC-48334) and zidovudine in patients with HIV-1 infection and 200-500 CD4 cells/mm3. , 1994, Journal of acquired immune deficiency syndromes.

[12]  N. Weinreb.  Interruption in enzyme replacement therapy for gaucher disease , 2001, British journal of haematology.

[13]  R. Van Tiggelen,et al.  Gaucher disease , 2019, Haematology.

[14]  E. Levy-Lahad,et al.  Replacement therapy with imiglucerase for type 1 Gaucher's disease , 1995, The Lancet.

[15]  P. Meikle,et al.  Prevalence of lysosomal storage disorders. , 1999, JAMA.

[16]  J. Aerts,et al.  Low-dose N-butyldeoxynojirimycin (OGT 918) for type I Gaucher disease. , 2002, Blood cells, molecules & diseases.

[17]  M. Pocovi,et al.  Report of the Spanish Gaucher's disease registry: clinical and genetic characteristics. , 2000, Haematologica.

[18]  P. Kaplan,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. , 2002, The American journal of medicine.

[19]  R. Brady,et al.  METABOLISM OF GLUCOCEREBROSIDES. II. EVIDENCE OF AN ENZYMATIC DEFICIENCY IN GAUCHER'S DISEASE. , 1965, Biochemical and biophysical research communications.

[20]  K. Sims,et al.  Quality of life assessment in adults with type 1 Gaucher disease , 1999, Quality of Life Research.

[21]  D. Häussinger,et al.  Correlation of bone marrow response with hematological, biochemical, and visceral responses to enzyme replacement therapy of nonneuronopathic (type 1) Gaucher disease in 30 adult patients. , 2002, Blood cells, molecules & diseases.

[22]  E. Beutler,et al.  Glucocerebrosidase (Gaucher disease) , 1996, Human mutation.

[23]  J. Aerts.  The European Working Group on Gaucher Disease , 1996 .

[24]  J. Dambrosia,et al.  Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. , 1995, Pediatrics.

[25]  K. Sandhoff,et al.  Partial enzyme deficiencies: residual activities and the development of neurological disorders. , 1983, Developmental neuroscience.

[26]  M. Itzchaki,et al.  Effect of low-dose enzyme replacement therapy on bones in Gaucher disease patients with severe skeletal involvement. , 1996, Blood cells, molecules & diseases.

[27]  A. Knudson,et al.  Genetics of the Sphingolipidoses1 , 1962 .

[28]  D. Häussinger,et al.  Clinical monitoring after cessation of enzyme replacement therapy in m. gaucher , 2001, British journal of haematology.

[29]  M. Prins,et al.  The natural course of Gaucher disease in The Netherlands: Implications for monitoring of disease manifestations , 2000, Journal of Inherited Metabolic Disease.

[30]  D. Balicki,et al.  The clinical course of treated and untreated Gaucher disease. A study of 45 patients. , 1995, Blood cells, molecules & diseases.

[31]  M. Horowitz,et al.  Low-dose enzyme replacement therapy for Gaucher's disease: effects of age, sex, genotype, and clinical features on response to treatment. , 1994, The American journal of medicine.

[32]  J. McPherson,et al.  Antibody response in patients with Gaucher disease after repeated infusion with macrophage-targeted glucocerebrosidase. , 1993, Blood.

[33]  Mario Maas,et al.  Substrate reduction therapy of glycosphingolipid storage disorders , 2006, Journal of Inherited Metabolic Disease.

[34]  A. Damiano,et al.  The health-related quality of life of adults with Gaucher's disease receiving enzyme replacement therapy: results from a retrospective study , 1998, Quality of Life Research.

[35]  E. Beutler,et al.  Failure of Alglucerase Infused into Gaucher Disease Patients to Localize in Marrow Macrophages , 1995, Molecular medicine.

[36]  C. Hollak,et al.  4 Plasma and metabolic abnormalities in Gaucher's disease , 1997 .

[37]  M. Horowitz,et al.  Gaucher's disease: molecular, genetic and enzymological aspects. , 1997, Bailliere's clinical haematology.

[38]  E. Levy-Lahad,et al.  Gaucher's disease: genetic counselling and population screening. , 1997, Bailliere's clinical haematology.

[39]  R. Brady,et al.  Mutation analysis of the acid beta-glucosidase gene in a patient with type 3 Gaucher disease and neutralizing antibody to alglucerase. , 2001, Mutation research.

[40]  B. Bembi,et al.  Management of neuronopathic Gaucher disease: A European consensus , 2001, Journal of Inherited Metabolic Disease.

[41]  T. Cox,et al.  3 Gaucher's disease: clinical features and natural history , 1997 .

[42]  A. Saven,et al.  Gaucher Disease: Clinical, Laboratory, Radiologic, and Genetic Features of 53 Patients , 1992, Medicine.

[43]  A. Lahad,et al.  High prevalence of low serum vitamin B12 in a multi‐ethnic Israeli population , 2001, British journal of haematology.

[44]  C. Hollak,et al.  Dixon quantitative chemical shift imaging is a sensitive tool for the evaluation of bone marrow responses to individualized doses of enzyme supplementation therapy in type 1 Gaucher disease. , 2001, Blood cells, molecules & diseases.

[45]  T. Merigan,et al.  The tolerability and pharmacokinetics of N-butyl-deoxynojirimycin in patients with advanced HIV disease (ACTG 100). The AIDS Clinical Trials Group (ACTG) of the National Institute of Allergy and Infectious Diseases. , 1995, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.