Review of miglustat for clinical management in Gaucher disease type 1

Can Ficicioglu

The Children’s Hospital of Philadelphia, Section of Biochemical Genetics

Abstract: Gaucher disease is a progressive lysosomal storage disorder caused by the deficiency of glucocerebrosidase, and characterized by intralysosomal storage of glucosylceramide that leads to dysfunction in multiple organ systems. Intravenous enzyme replacement with imiglucerase is the accepted standard for treatment of symptomatic patients and has been effective in reducing many of the signs and symptoms of type I Gaucher disease in the majority of patients without serious adverse effects. An alternative therapeutic approach is substrate reduction therapy with N-butyldeoxynojirimycin (NB-DNJ) (miglustat; Zavesca^®), an imino sugar that reversibly inhibits glucosylceremide synthase and reduces intracellular storage of glucosylceramide. Miglustat was recently approved in Europe and the United States for symptomatic patients with mild to moderate clinical manifestations for whom enzyme replacement therapy is not an option. This review article discusses the results of clinical studies and use of miglustat as a therapeutic agent in patients with type I Gaucher disease.

Keywords: Gaucher disease, miglustat, substrate reduction therapy