治疗高脂蛋白血症的分子疗法正在发展中。

IF 4.1 3区 医学 Q1 GENETICS & HEREDITY
Molecular Diagnosis & Therapy Pub Date : 2025-05-01 Epub Date: 2025-01-28 DOI:10.1007/s40291-024-00768-0
Maud Ahmad, Robert A Hegele
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引用次数: 0

摘要

高脂蛋白血症引起的临床终点包括动脉粥样硬化性心血管疾病和急性胰腺炎。针对蛋白转化酶枯草杆菌素/结蛋白9 (PCSK9)、脂蛋白(a)、载脂蛋白C-III和血管生成素样蛋白3的新兴降脂疗法代表了高脂蛋白血症患者管理的有希望的进展。这些疗法为降低致病性脂质和脂蛋白种类提供了新方法,特别是对于那些常规治疗无法充分控制或无法耐受的严重紊乱患者。这些新型治疗药物的分子靶点是通过遗传流行病学研究确定和验证的。蛋白转化酶枯草杆菌素/酮素9抑制剂(如单克隆抗体和小干扰RNA)通过显著降低低密度脂蛋白胆固醇水平和主要心血管事件,彻底改变了高胆固醇血症的管理。对PCSK9进行基因组编辑有望为家族性高胆固醇血症患者提供潜在的治疗方法。一些研究性脂蛋白(a)靶向治疗旨在降低动脉粥样硬化性心血管疾病和主动脉瓣疾病的风险,尽管明确的临床终点研究仍有待完成。olezarsen和plzasiran对APOC3信使RNA表达的抑制可显著降低家族性乳糜小铁血症综合征患者血浆甘油三酯水平,并显著降低胰腺炎风险。最后,单克隆抗体evinacumab抑制血管生成素样蛋白3已经改变了纯合子家族性高胆固醇血症患者的管理。总之,这些新型药物扩大了治疗缓存,为高风险高脂蛋白血症患者提供个性化的降脂策略,改善临床结果并解决以前未满足的医疗需求。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular Therapeutics in Development to Treat Hyperlipoproteinemia.

Clinical endpoints caused by hyperlipoproteinemia include atherosclerotic cardiovascular disease and acute pancreatitis. Emerging lipid-lowering therapies targeting proprotein convertase subtilisin/kexin 9 (PCSK9), lipoprotein(a), apolipoprotein C-III, and angiopoietin-like protein 3 represent promising advances in the management of patients with hyperlipoproteinemia. These therapies offer novel approaches for lowering pathogenic lipid and lipoprotein species, particularly in patients with serious perturbations who are not adequately controlled with conventional treatments or who are unable to tolerate them. Molecular targets for these novel therapeutic agents were identified and validated through genetic epidemiology studies. Proprotein convertase subtilisin/kexin 9 inhibitors (e.g., monoclonal antibodies and small interfering RNA) have revolutionized hypercholesterolemia management by significantly reducing both low-density lipoprotein cholesterol levels and major cardiovascular events. Genome editing of PCSK9 promises to provide a potential cure for patients with familial hypercholesterolemia. Several investigational lipoprotein(a)-targeting therapies aim to reduce the risk of atherosclerotic cardiovascular disease and aortic valve disease, although definitive clinical endpoint studies remain to be completed. Inhibition of APOC3 messenger RNA expression by olezarsen and plozasiran significantly lowers plasma triglyceride levels and markedly reduces pancreatitis risk in patients with familial chylomicronemia syndrome. Finally, angiopoietin-like protein 3 inhibition by the monoclonal antibody evinacumab has transformed management of patients with homozygous familial hypercholesterolemia. Together, these novel agents expand the therapeutic cache, offering personalized lipid-lowering strategies for high-risk patients with hyperlipoproteinemia, improving clinical outcomes and addressing previously unmet medical needs.

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来源期刊
CiteScore
7.80
自引率
2.50%
发文量
53
审稿时长
>12 weeks
期刊介绍: Molecular Diagnosis & Therapy welcomes current opinion articles on emerging or contentious issues, comprehensive narrative reviews, systematic reviews (as outlined by the PRISMA statement), original research articles (including short communications) and letters to the editor. All manuscripts are subject to peer review by international experts.
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