Type 1 Gaucher disease (GD1) is an autosomal recessive lysosomal storage disorder
associated with abnormal accumulation of glucocerebrosides. Plasma total cholesterol
(TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol
(HDL-c) are decreased in GD1 patients. The effects of substrate reduction therapy
(SRT) with miglustat on plasma lipids and atherogenic factors have not yet been examined.
Here, we report plasma atherogenic profile data from GD1 patients undergoing long-term
Plasma was analysed in 26 GD1 patients treated with miglustat for up to 36 months.
Ten patients were therapy-naïve and 16 had switched from enzyme replacement therapy
(ERT); the interval between stopping ERT and starting SRT was 2-6 weeks. Plasma TC,
triglycerides (TG), LDL-c, HDL-c, apolipoproteins (apoA-I, apoB, and Lp[a]), C-reactive
protein (CRP) concentrations, and chitotriosidase activity were measured before SRT
(baseline) and at 12, 24, and 36 months follow up.
In therapy-naïve patients, miglustat significantly increased plasma HDL-c and apoA-I,
and slightly increased TC; while TG, CRP concentrations, and TC/HDL-c ratios decreased
significantly after 24 months. In contrast, there were no changes in HDL-c and apoA-I,
or in the TC/HDL-c ratio in switch patients. However, a decrease in CRP was observed
after 12 months. LDL-c and apoB were not significantly altered in either patient group.
Miglustat appears to have beneficial effects on plasma lipid, lipoprotein, and CRP
concentrations in therapy-naïve GD1 patients, resulting in an improved atherogenic
lipid profile. Further studies are required to determine the effect of miglustat on
coronary heart disease risk.
Copyright 2009 Elsevier Ireland Ltd. All rights reserved.