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Purpose of review <p>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 <i>APOC3</i> and angiopoietin-like protein 3 (<i>ANGPTL3</i>).</p> Recent findings <p>Volanesorsen, an ASO targeting <i>APOC3</i>, has shown effectiveness in managing FCS, multifactorial chylomicronemia, and familial partial lipodystrophy, but its use is limited by thrombocytopenia. Emerging therapies, Olezarsen (ASO anti-<i>APOC3</i>) and Plozasiran (siRNA anti-<i>APOC3</i>), 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.</p> Summary <p>Suppressing <i>APOC3</i> 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.</p>

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Novel Therapeutics for Familial Chylomicronemia Syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月21日

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  • Maria Cristina Izar,
  • Francisco Antonio Helfenstein Fonseca

摘要

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.

Summary

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.