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脂质代谢紊乱和动脉粥样硬化的生物治疗进展。

Advances in biological therapies for dyslipidemias and atherosclerosis.

机构信息

4th Department of Internal Medicine, Clinical Genomics and Pharmacogenomics Unit, 'Attikon' Hospital, Medical School, National and Kapodistrian University of Athens, Greece; Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Greece; Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Laboratory of Biochemistry, University of Crete Medical School Heraklion, Greece.

出版信息

Metabolism. 2021 Mar;116:154461. doi: 10.1016/j.metabol.2020.154461. Epub 2020 Dec 5.

Abstract

Atherosclerosis is a multifactorial disease influenced by genetics, lifestyle and environmental factors. Despite therapeutic advances that reduce the risk of cardiovascular events, atherosclerosis-related diseases remain the leading cause of mortality worldwide. Precise targeting of genes involved in lipoprotein metabolism is an emerging approach for atherosclerosis prevention and treatment. This article focuses on the latest developments, clinical potential and current challenges of monoclonal antibodies, vaccines and genome/transcriptome modification strategies, including antisense oligonucleotides, genome/base editing and gene therapy. Multiple lipid lowering biological therapies have already been approved by the FDA with impressive results to date, while many more promising targets are being pursued in clinical trials or pre-clinical animal models.

摘要

动脉粥样硬化是一种受遗传、生活方式和环境因素影响的多因素疾病。尽管治疗学的进步降低了心血管事件的风险,但与动脉粥样硬化相关的疾病仍然是全球死亡的主要原因。精确靶向参与脂蛋白代谢的基因是动脉粥样硬化预防和治疗的新兴方法。本文重点介绍了单克隆抗体、疫苗和基因组/转录组修饰策略(包括反义寡核苷酸、基因组/碱基编辑和基因治疗)的最新进展、临床潜力和当前挑战。目前,已有多种降脂生物疗法获得 FDA 批准,且疗效显著,而更多有前途的靶点正在临床试验或临床前动物模型中进行研究。

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