Department of Vascular Medicine, Academic Medical Center Amsterdam, The Netherlands.
J Lipid Res. 2010 May;51(5):1057-62. doi: 10.1194/jlr.M002915. Epub 2009 Dec 14.
To investigate the impact of mipomersen, an apolipoprotein B-100 (apoB) synthesis inhibitor, on intra-hepatic triglyceride content (IHTG content), we conducted a randomized, double-blind, placebo-controlled study in 21 patients with familial hypercholesterolemia (FH). Subjects received a weekly subcutaneous dose of 200 mg mipomersen or placebo for 13 weeks while continuing conventional lipid lowering therapy. The primary endpoint was change in IHTG content from week 0 to week 15 as measured by localized proton magnetic resonance spectroscopy (1H-MRS). Thirteen weeks of mipomersen administration reduced LDL-cholesterol by 22.0 (17.8) % and apoB by 19.9 (17.4) % (both P < 0.01). One of 10 patients (10%) in the mipomersen-treated group developed mild hepatic steatosis at week 15, which was reversible following mipomersen discontinuation. For the group, there was a trend toward an increase in IHTG content [placebo; baseline: 1.2% and week 15: 1.1%; change -0.1 (0.9). Mipomersen; baseline: 1.2% and week 15: 2.1%; change 0.8 (1.7) (P = 0.0513)]. Mipomersen administration for 13 weeks to subjects with FH is associated with a trend toward an increase in IHTG content. Future studies evaluating the effects of long-term use of mipomersen reaching more profound reductions in apoB are required prior to broader use of this compound.
为了研究载脂蛋白 B-100（apoB）合成抑制剂米泊美生对肝内甘油三酯含量（IHTG 含量）的影响，我们在 21 例家族性高胆固醇血症（FH）患者中进行了一项随机、双盲、安慰剂对照研究。受试者接受每周 200mg 米泊美生或安慰剂皮下注射，共 13 周，同时继续常规降脂治疗。主要终点为 1H-MRS 测量的从第 0 周至第 15 周 IHTG 含量的变化。米泊美生治疗 13 周可使 LDL-胆固醇降低 22.0（17.8）%，apoB 降低 19.9（17.4）%（均 P < 0.01）。米泊美生治疗组 10 例患者中有 1 例（10%）在第 15 周发生轻度肝脂肪变性，米泊美生停药后可逆转。对于该组，IHTG 含量有增加的趋势[安慰剂；基线：1.2%，第 15 周：1.1%；变化-0.1（0.9）。米泊美生；基线：1.2%，第 15 周：2.1%；变化 0.8（1.7）（P = 0.0513）]。FH 患者接受米泊美生治疗 13 周与 IHTG 含量增加趋势相关。在更广泛使用这种化合物之前，需要进行评估米泊美生长期使用对 apoB 产生更显著降低作用的影响的研究。
