Novel Therapeutics for Familial Chylomicronemia Syndrome.

IF 5.7 2区医学 Q1 PERIPHERAL VASCULAR DISEASE

Current Atherosclerosis Reports Pub Date : 2025-04-21 DOI:10.1007/s11883-025-01295-x

Maria Cristina Izar, Francisco Antonio Helfenstein Fonseca

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引用次数: 0

Abstract

Purpose of review: This review discusses new treatment approaches for familial chylomicronemia syndrome (FCS), a rare disorder affecting triglyceride metabolism. The focus is on antisense oligonucleotides (ASO) and small-interfering RNA (siRNA) therapies targeting APOC3 and angiopoietin-like protein 3 (ANGPTL3).

Recent findings: Volanesorsen, an ASO targeting APOC3, has shown effectiveness in managing FCS, multifactorial chylomicronemia, and familial partial lipodystrophy, but its use is limited by thrombocytopenia. Emerging therapies, Olezarsen (ASO anti-APOC3) and Plozasiran (siRNA anti-APOC3), both conjugated with GalNAc, show promise in reducing acute pancreatitis risk without platelet concerns. ANGPTL3 inhibition requires residual lipoprotein lipase (LPL) activity, with only siRNA-based therapies-zodasiran and solbinsiran-under investigation. Suppressing APOC3 expression and targeting ANGPTL3 via siRNA offer significant potential, but long-term studies are needed to confirm their efficacy and safety. Future research may explore gene-editing strategies using lipid nanoparticle-based CRISPR-Cas9 delivery for more durable treatment outcomes.

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家族性乳糜微粒血症综合征的新疗法。

综述目的：本综述讨论了家族性乳糜小铁血症综合征（FCS）的新治疗方法，这是一种影响甘油三酯代谢的罕见疾病。重点是针对APOC3和血管生成素样蛋白3 （ANGPTL3）的反义寡核苷酸（ASO）和小干扰RNA （siRNA）疗法。最近的发现：Volanesorsen，一种靶向APOC3的ASO，在治疗FCS、多因子乳糜小红细胞血症和家族性部分脂肪营养不良方面显示出有效性，但其使用受到血小板减少症的限制。新兴疗法Olezarsen （ASO抗apoc3）和plzasiran （siRNA抗apoc3）均与GalNAc偶联，有望降低急性胰腺炎风险，而无需担心血小板。抑制ANGPTL3需要残余脂蛋白脂肪酶（LPL）活性，目前仅研究了基于sirna的疗法-zodasiran和solbinsiran。抑制APOC3表达和通过siRNA靶向ANGPTL3具有巨大的潜力，但其有效性和安全性需要长期研究来证实。未来的研究可能会探索基于脂质纳米颗粒的CRISPR-Cas9递送的基因编辑策略，以获得更持久的治疗效果。

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

Current Atherosclerosis Reports 医学-

CiteScore

9.00

自引率

3.40%

发文量

审稿时长

6-12 weeks

期刊介绍： The aim of this journal is to systematically provide expert views on current basic science and clinical advances in the field of atherosclerosis and highlight the most important developments likely to transform the field of cardiovascular prevention, diagnosis, and treatment. We accomplish this aim by appointing major authorities to serve as Section Editors who select leading experts from around the world to provide definitive reviews on key topics and papers published in the past year. We also provide supplementary reviews and commentaries from well-known figures in the field. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.