Novel Therapeutics for Familial Chylomicronemia Syndrome
Maria Cristina de Oliveira Izar, Francisco Antônio Helfenstein Fonseca
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.