摘要
升高的甘油三酯水平(超过1000毫克/升)与增加胰腺炎的风险有关。载脂蛋白-CIII(apoC-III)在甘油三酯和富含甘油三酯脂蛋白的代谢中起着关键作用。载脂蛋白C-Ⅲ(APOC 3)基因缺失与低甘油三酯水平及心血管疾病(CVD)风险降低有关,而APOC 3过度表达则与高甘油三酯血症有关。虽然许多药物,如纤维蛋白、他汀类和欧米茄-3脂肪酸会适度降低甘油三酯水平(以及载脂蛋白-Ⅲ的浓度),但仍有许多患者仍有严重的高甘油三酯血症,并有可能患上胰腺炎和CVD。针对APOC3mRNA的反义寡核苷酸(以前称为ISIS 304801,IIS-APOCIIIRx和Ionis-APOCIIIRx)显著降低了APOC-III的产量和甘油三酯的浓度,目前正在第三阶段试验中进行评估。在本文的叙述中,我们提出了目前可用的临床证据,证明伏拉尼森治疗高甘油三酯血症的有效性和安全性。
关键词: 反义寡核苷酸、载脂蛋白C-Ⅲ、高甘油三酯血症、Ionis-APOCIIIRx、ISIS 304801、ISS-APOCIIIRx、甘油三酯、伏拉尼森。
Current Medicinal Chemistry
Title:APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia
Volume: 25 Issue: 13
关键词: 反义寡核苷酸、载脂蛋白C-Ⅲ、高甘油三酯血症、Ionis-APOCIIIRx、ISIS 304801、ISS-APOCIIIRx、甘油三酯、伏拉尼森。
摘要: Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) is associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review, we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
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APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia, Current Medicinal Chemistry 2018; 25 (13) . https://dx.doi.org/10.2174/0929867324666170609081612
DOI https://dx.doi.org/10.2174/0929867324666170609081612 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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