Dávalos Alberto, Chroni Angeliki
Laboratory of Disorders of Lipid Metabolism and Molecular Nutrition, Madrid Institute for Advanced Studies (IMDEA)-Food, Ctra. de Cantoblanco 8, 28049, Madrid, Spain,
Handb Exp Pharmacol. 2015;224:649-89. doi: 10.1007/978-3-319-09665-0_22.
The specificity of Watson-Crick base pairing and the development of several chemical modifications to oligonucleotides have enabled the development of novel drug classes for the treatment of different human diseases. This review focuses on promising results of recent preclinical or clinical studies on targeting HDL metabolism and function by antisense oligonucleotides and miRNA-based therapies. Although many hurdles regarding basic mechanism of action, delivery, specificity, and toxicity need to be overcome, promising results from recent clinical trials and recent approval of these types of therapy to treat dyslipidemia suggest that the treatment of HDL dysfunction will benefit from these unique clinical opportunities. Moreover, an overview of monoclonal antibodies (mAbs) developed for the treatment of dyslipidemia and cardiovascular disease and currently being tested in clinical studies is provided. Initial studies have shown that these compounds are generally safe and well tolerated, but ongoing large clinical studies will assess their long-term safety and efficacy.
沃森-克里克碱基配对的特异性以及对寡核苷酸的多种化学修饰的发展，使得开发用于治疗不同人类疾病的新型药物类别成为可能。本综述重点关注近期关于通过反义寡核苷酸和基于miRNA的疗法靶向高密度脂蛋白（HDL）代谢和功能的临床前或临床研究的有前景的结果。尽管在作用机制、递送、特异性和毒性等基本方面仍有许多障碍需要克服，但近期临床试验的有前景结果以及这类疗法近期被批准用于治疗血脂异常表明，HDL功能障碍的治疗将从这些独特的临床机遇中受益。此外，还提供了为治疗血脂异常和心血管疾病而开发且目前正在临床研究中进行测试的单克隆抗体（mAb）的概述。初步研究表明这些化合物总体上安全且耐受性良好，但正在进行的大型临床研究将评估它们的长期安全性和疗效。
