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Inhibition of angiopoietin-like protein 3 as a target for managing hypertriglyceridemia
Pablo Corral1,2, Natalia Nardelli3, Laura Schreier4
1FASTA University, Pharmacology and Research Department.
Purpose Of Review:
To summarize recent advances in therapeutic strategies targeting angiopoietin-like protein 3 (ANGPTL3), a central regulator of triglyceride and remnant lipoprotein metabolism, and to discuss the potential of emerging pharmacologic approaches.
Recent Findings:
Several pharmacologic approaches have demonstrated robust lipid-lowering efficacy through ANGPTL3 inhibition. Monoclonal antibodies (evinacumab, SHR-1918) and RNA-based therapies (vupanorsen, zodasiran, solbinsiran) effectively reduce triglycerides, apoprotein B (apoB)-containing lipoproteins, and nonhigh-density lipoprotein cholesterol. The newest and most promising innovation is CRISPR-mediated disruption of ANGPTL3 (CTX310).
Summary:
ANGPTL3 inhibition represents one of the most powerful current strategies for lowering triglyceride-rich lipoproteins and residual cardiovascular risk. While monoclonal antibodies and RNA-based drugs offer effective, repeat-dose therapies, in vivo CRISPR editing could enable a one-time, lifelong correction of hypertriglyceridemia and mixed dyslipidemia. The main challenge ahead lies in ensuring safety, scalability, and equitable access if long-term efficacy and tolerability are confirmed in phase 3 trials.
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