Abstract
Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) is associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review, we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
Keywords: Antisense oligonucleotides, apolipoprotein C-III, hypertriglyceridemia, IONIS-ApoCIIIRx, ISIS 304801, ISIS-ApoCIIIRx, triglycerides, volanesorsen.
Current Medicinal Chemistry
Title:APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia
Volume: 25 Issue: 13
Author(s): Joel Schmitz and Ioanna Gouni-Berthold*
Affiliation:
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine (PEDP), University of Cologne, Kerpener Str. 62, 50937 Cologne,Germany
Keywords: Antisense oligonucleotides, apolipoprotein C-III, hypertriglyceridemia, IONIS-ApoCIIIRx, ISIS 304801, ISIS-ApoCIIIRx, triglycerides, volanesorsen.
Abstract: Elevated triglyceride levels (higher than ~1000 mg/dL) are associated with an increased risk for pancreatitis. Apolipoprotein-CIII (apoC-III) plays a key role in the metabolism of triglycerides and triglyceride-rich lipoproteins. Loss of function mutations in the gene encoding apoC-III (APOC3) is associated with low triglyceride levels and a decreased risk for cardiovascular disease (CVD) while overexpression of APOC3 is associated with hypertriglyceridemia. Although many drugs such as fibrates, statins and omega-3 fatty acids modestly decrease triglyceride levels (and apoC-III concentrations), there are many patients who still have severe hypertriglyceridemia and are at increased risk for pancreatitis and potentially for CVD. The antisense oligonucleotide (ASO) against APOC3 mRNA volanesorsen (previously called ISIS 304801, ISIS-ApoCIIIRx and IONIS-ApoCIIIRx) robustly decreases both, apoC-III production and triglyceride concentrations and is being currently evaluated in phase 3 trials. In this narrative review, we present the currently available clinical evidence on the efficacy and safety of volanesorsen for the treatment of hypertriglyceridemia.
Export Options
About this article
Cite this article as:
Schmitz Joel and Gouni-Berthold Ioanna *, APOC-III Antisense Oligonucleotides: A New Option for the Treatment of Hypertriglyceridemia, Current Medicinal Chemistry 2018; 25 (13) . https://dx.doi.org/10.2174/0929867324666170609081612
DOI https://dx.doi.org/10.2174/0929867324666170609081612 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
CCL17/Thymus and Activation-Related Chemokine: A biomarker for Churg-Strauss Syndrome?
Current Biomarkers (Discontinued) Phosphodiesterase Inhibitors as Potential Cognition Enhancing Agents
Current Topics in Medicinal Chemistry Expression and Function of Cytokines and Chemokines in Neuropsychiatric Related Systemic Lupus Erythematosus
Current Rheumatology Reviews Cardiovascular Disease Burden and Risk Factors Before and After Kidney Transplant
Cardiovascular & Hematological Disorders-Drug Targets Neuroimaging Features of Acquired Metabolic and Toxic Encephalopathies
Current Medical Imaging The Lung Disease of Rheumatoid Arthritis
Current Respiratory Medicine Reviews Current Update on Eosinophilic Lung Diseases and Anti-IL-5 Treatment
Recent Patents on Anti-Infective Drug Discovery Mouse Models of Autoimmune Uveitis
Current Pharmaceutical Design Adverse Drug Reactions: Trends in a Tertiary Care Hospital
Current Drug Safety New Pharmacological Approaches to the Prevention of Myocardial Ischemia- Reperfusion Injury
Current Drug Targets Behcets Syndrome: Literature Review
Current Rheumatology Reviews Colchicine: An Old Wine in a New Bottle?
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cellular Membrane Microparticles: Potential Targets of Combinational Therapy for Vascular Disease
Current Vascular Pharmacology Novel Strategies in the Treatment of Pulmonary Arterial Hypertension
Current Drug Targets Update on Medical and Surgical Management of Intracerebral Hemorrhage
Reviews on Recent Clinical Trials Drugs, Trials and Pathogenesis: Will Connecting these Help us Understand SLE?
Current Rheumatology Reviews The Role of Melanin to Dissociate Oxygen from Water to Treat Retinopathy of Prematurity
Central Nervous System Agents in Medicinal Chemistry MCP-1/CCL2 as a Therapeutic Target in Myocardial Infarction and Ischemic Cardiomyopathy
Inflammation & Allergy - Drug Targets (Discontinued) Rheumatoid Foot and Ankle Surgery
Current Rheumatology Reviews Ischemic Colitis: Current Diagnosis and Treatment
Current Drug Targets