Messenger interference RNA therapies targeting apolipoprotein C-III and angiopoietin-like protein 3 for mixed hyperlipidemia: the future of plozasiran and zodasiran.

IF 3.6 3区医学 Q2 PHARMACOLOGY & PHARMACY

Expert Review of Clinical Pharmacology Pub Date : 2024-11-03 DOI:10.1080/17512433.2024.2423724

Zonghao Pan, Muhammad Adnan Zaman, Sidra Kalsoom, Yani Zhang

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引用次数: 0

Abstract

Introduction: Mixed hyperlipidemia represents a substantial public health issue and a considerable burden on healthcare systems. Although the introduction of statins and LDL-cholesterol lowering agents have significantly reduced the incidence of atherosclerotic cardiovascular diseases (ASCVD), a significant portion of the population continues to exhibit ASCVD progression due to elevated triglyceride-rich lipoprotein (TRL) levels. This persistent risk has catalyzed the development of novel pharmacological interventions targeting these lipoproteins.

Areas covered: Our special report commenced with a targeted PubMed search using keywords such as 'plozasiran,' 'zodasiran,' and terms related to APOC3 and ANGPTL3. As the review progressed, emergent research questions guided further searches, allowing for the inclusion of additional relevant articles to comprehensively illustrate the linkage between TRLs and cardiovascular disease, discuss the roles of APOC3, ANGPTL3, and the pharmaceutical agents that target these proteins, and provide a comparison on the ARCHES-2 and MUIR trials.

Expert opinion: The ARCHES-2 and MUIR trials demonstrated effective triglyceride reduction by these therapies, yet it is uncertain if this correlates with significant clinical benefits. Advances in antisense oligonucleotide technology, especially the GalNAc delivery platform, show promise for personalized lipid management, though challenges such as cost and safety concerns remain.

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针对脂蛋白 C-III 和血管生成素样蛋白 3 的信使干扰 RNA疗法治疗混合型高脂血症：plozasiran 和 zodasiran 的未来。

导言：混合型高脂血症是一个重大的公共卫生问题，也是医疗系统的沉重负担。尽管他汀类药物和降低低密度脂蛋白胆固醇药物的引入大大降低了动脉粥样硬化性心血管疾病（ASCVD）的发病率，但由于富含甘油三酯的脂蛋白（TRLs）水平升高，仍有相当一部分人群的 ASCVD 病情持续恶化。这种持续存在的风险促进了针对这些脂蛋白的新型药物干预措施的开发：我们的特别报告首先使用 "plozasiran"、"zodasiran "等关键词以及与 APOC3 和 ANGPTL3 相关的术语在 PubMed 上进行了有针对性的搜索。随着综述的深入，新出现的研究问题引导了进一步的搜索，从而纳入了更多的相关文章，以全面说明TRL与心血管疾病之间的联系，讨论APOC3、ANGPTL3和针对这些蛋白的药物的作用，并对ARCHES-2和MUIR试验进行比较：ARCHES-2和MUIR试验表明，这些疗法能有效降低甘油三酯，但还不能确定这是否与显著的临床疗效相关。反义寡核苷酸技术的进步，尤其是 GalNAc 递送平台，为个性化血脂管理带来了希望，但成本和安全性等挑战依然存在。

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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来源期刊

Expert Review of Clinical Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.30

自引率

2.30%

发文量

127

期刊介绍： Advances in drug development technologies are yielding innovative new therapies, from potentially lifesaving medicines to lifestyle products. In recent years, however, the cost of developing new drugs has soared, and concerns over drug resistance and pharmacoeconomics have come to the fore. Adverse reactions experienced at the clinical trial level serve as a constant reminder of the importance of rigorous safety and toxicity testing. Furthermore the advent of pharmacogenomics and ‘individualized’ approaches to therapy will demand a fresh approach to drug evaluation and healthcare delivery. Clinical Pharmacology provides an essential role in integrating the expertise of all of the specialists and players who are active in meeting such challenges in modern biomedical practice.