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 orally active 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.
Cox
T M
TM
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. jbg20@medschl.cam.ac.uk
Aerts
J M F G
JM
Andria
G
G
Beck
M
M
Belmatoug
N
N
Bembi
B
B
Chertkoff
R
R
Vom Dahl
S
S
Elstein
D
D
Erikson
A
A
Giralt
M
M
Heitner
R
R
Hollak
C
C
Hrebicek
M
M
Lewis
S
S
Mehta
A
A
Pastores
G M
GM
Rolfs
A
A
Miranda
M C Sa
MC
Zimran
A
A
D002986:Clinical Trials as Topic; D057487:Enzyme Therapy; D005776:Gaucher Disease / Q000175:diagnosis / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans
D005962:Glucosylceramidase; C090568:imiglucerase