Gemcabene as a Potential Therapeutic for NASH: Lessons Learnt from its Clinical Trials in Dyslipidemia

D. Oniciu
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Abstract

Elevated hepatic lipogenesis and inflammation are associated with the progression of non-alcoholic steatohepatitis (NASH) and cardiovascular disease. Gemcabene, a small molecule in development for dyslipidemia, reduces plasma very low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and C-reactive protein (CRP) in animal models and humans. An analysis of the clinical information available for gemcabene and translational research substantiates the potential of gemcabene as a therapeutic agent for NASH. Specifically, gemcabene showed positive effects in clinical trials in severe hypertriglyceridemia and in subsets of obese, diabetic patients, particularly reductions in triglycerides, cholesterol and proatherogenic and inflammation markers. In nonclinical models, gemcabene showed significant improvement in non-alcoholic fatty liver disease (NAFLD) activity and fibrosis scores and affected beneficially the hepatic expression of many lipid regulating and inflammatory genes.
Gemcabene作为NASH的潜在治疗药物:从其血脂异常临床试验中获得的经验教训
肝脏脂肪生成和炎症升高与非酒精性脂肪性肝炎(NASH)和心血管疾病的进展有关。Gemcabene是一种用于治疗血脂异常的小分子药物,可在动物模型和人类中降低血浆极低密度脂蛋白胆固醇(VLDL-C)、低密度脂蛋白胆固醇(LDL-C)、甘油三酯(TG)和c反应蛋白(CRP)。对gemcabene的临床信息和转化研究的分析证实了gemcabene作为NASH治疗剂的潜力。具体而言,gemcabene在严重高甘油三酯血症和肥胖、糖尿病患者亚群的临床试验中显示出积极作用,特别是在甘油三酯、胆固醇、促动脉粥样硬化和炎症标志物方面的降低。在非临床模型中,gemcabene显示出非酒精性脂肪性肝病(NAFLD)活性和纤维化评分的显著改善,并有益地影响了许多脂质调节和炎症基因的肝脏表达。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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