Related Experiment Videos
Olezarsen for the Treatment of Hypertriglyceridemia
Antonio Sebastian Hernandez Rodriguez1, Toshifumi Yokota2,3
1Department of Medical Genetics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Abstract:
Hypertriglyceridemia (HTG) is a common dyslipidemic disorder characterized by fasting serum triglyceride (TG) concentrations exceeding 150 mg/dL. Elevated TG levels contribute substantially to cardiovascular risk, as remnant lipoprotein particles derived from triglyceride-rich lipoproteins (TRL) exhibit marked atherogenicity. Conventional therapies, such as statins and fibrates, often fail to adequately lower TG levels or improve clinical outcomes. Advances in antisense technology have enabled the development of precise oligonucleotide-based therapies that reduce TG levels by targeting key regulators of lipid metabolism. Apolipoprotein C-III (ApoC-III) is a key regulator of TLR clearance, positioning it as a critical therapeutic target. Olezarsen, a next-generation N-acetylgalactosamine-conjugated antisense oligonucleotide (ASO) designed to induce RNase H-mediated degradation of APOC3 mRNA, received FDA approval in December 2024 as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). In this chapter, we review the pharmacological mechanism, clinical development, and safety profile of olezarsen for FCS and broader hypertriglyceridemia-related indications.
Related Concept Videos
Lipid-Lowering Drugs: Statins and Miscellaneous Agents
Atherosclerosis III: Management
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme (ECE). Of...
Antiepileptic Drugs: Potassium Channel Activators
Ezogabine has gained approval as an adjunctive treatment...
Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...