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Updated: Jul 15, 2025
Isolation of High-density Lipoproteins for Non-coding Small RNA Quantification
Published on: November 28, 2016
Updates in Small Interfering RNA for the Treatment of Dyslipidemias
S Carugo1,2, C R Sirtori3, G Gelpi2
1Department of Clinical Sciences and Community Health, Dyspnea Lab, Università degli Studi di Milano, Milan, Italy.
Insights
RNA-based therapies offer new hope for managing complex lipid disorders like dyslipidemia. These innovative treatments target difficult-to-manage conditions, improving cardiovascular health and reducing atherosclerotic cardiovascular disease risk.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pharmacology
Background:
- Atherosclerotic cardiovascular disease (ASCVD) remains a primary global cause of mortality.
- Many patients with dyslipidemia are undertreated, highlighting a need for advanced therapies.
- Beyond LDL-C, lipoprotein(a) and triglyceride-rich lipoproteins are critical in cardiovascular risk.
Purpose of the Study:
- To review the emerging role of RNA-based therapies in managing dyslipidemias.
- To discuss the potential of novel agents in reducing atherosclerotic cardiovascular disease (ASCVD) risk.
- To explore the application of RNA therapeutics for challenging lipid disorders.
Main Methods:
- Review of recent clinical trial data for RNA-based lipid-lowering agents.
- Analysis of safety and efficacy findings for siRNA therapies targeting LDL-C, lipoprotein(a), and triglycerides.
- Evaluation of pharmacodynamic profiles and dosing strategies.
Main Results:
- Inclisiran demonstrates long-term safety and efficacy in lowering LDL-C, with potential for cardiovascular event reduction.
- Olpasiran shows a dose-dependent reduction in lipoprotein(a) levels, suitable for 12-week administration.
- Emerging therapies like ARO-APOC3 and ARO-ANG3 effectively lower apoC-III and ANGPTL3, though still in early development.
Conclusions:
- RNA-based therapies, particularly siRNA, represent a promising new class of drugs for treating dyslipidemias.
- These agents offer targeted approaches for managing complex lipid profiles and reducing ASCVD risk.
- The development of RNA therapeutics is crucial for personalized risk management in cardiovascular disease.
Purpose Of Review:
Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders.
Recent Findings:
The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.
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