Goal-oriented therapy with miglustat in Gaucher disease.

BACKGROUND Gaucher disease (GD) is a highly heterogeneous disorder with multisystem involvement. Specific therapeutic goals for each manifestation of type 1 GD (GD1) were established in 2004 by an international panel of experts, to facilitate better management of GD1 patients. The goals were defined based on experience with enzyme replacement therapy (ERT) using imiglucerase. Miglustat, a small iminosugar, is the only commercially available substrate reduction therapy (SRT) for patients with GD1. Several clinical studies have demonstrated the beneficial effects of miglustat on cardinal disease manifestations of GD1. OBJECTIVE To review the currently available data on miglustat, and provide guidance on the attainment of the GD therapeutic goals with miglustat therapy. METHODS A literature search identified publications on miglustat using MEDLINE, HighWire Press, and Google Scholar databases. Articles were identified using the terms 'miglustat' and 'Gaucher disease type 1'. FINDINGS Improvements in hematological manifestations and organomegaly can be expected with miglustat therapy, with disease stabilization achievable over the long term. Recent data suggest that miglustat can maintain stability in patients with mild to moderate GD1 who have been previously treated with ERT. Miglustat may be beneficial with regards to bone manifestations, with reduction in the incidence of patients reporting bone pain and improvements in bone mineral density seen within the first 24 months of therapy. CONCLUSIONS Several of the therapeutic goals for patients with GD1 can be achieved with miglustat therapy. In select cases, miglustat can be considered an alternative to ERT for the treatment of patients with GD1. Long-term experience with the use of miglustat will help define its overall safety and efficacy; this information will be useful in determining the role of SRT using miglustat in the management of the general adult GD1 patient population.