Related Experiment Video
Updated: Apr 19, 2026
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
Proprotein convertase subtilisin kexin 9 inhibitors: next generation in lipid-lowering therapy
Haralampos Milionis1, George Liamis, Moses Elisaf
1University of Ioannina, School of Medicine, Department of Internal Medicine , 451 10 Ioannina , Greece.
Insights
New PCSK9 inhibitors offer significant LDL-C reduction for hyperlipidemia patients, especially those unresponsive to statins. These subcutaneous therapies show promise for managing cardiovascular disease risk.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Lipidology
Background:
- Statins are primary treatments for hyperlipidemia and atherosclerotic cardiovascular disease (CVD) prevention by lowering LDL-C.
- A need exists for more effective LDL-C reduction in severe hypercholesterolemia and statin-intolerant patients.
Purpose of the Study:
- To explore novel therapeutic strategies for lowering LDL-C.
- To evaluate emerging treatments targeting PCSK9 for hyperlipidemia management.
Main Methods:
- Investigated PCSK9 inhibition via monoclonal antibodies (e.g., AMG145, REGN727, RN316).
- Reviewed Phase I-III clinical trials assessing these antibodies in high CVD risk patients.
Main Results:
- Monoclonal antibodies targeting PCSK9 demonstrated substantial LDL-C and apoB lowering effects.
- These agents are administered subcutaneously, offering an alternative delivery method.
Conclusions:
- PCSK9 inhibitors show significant efficacy alone or with statins.
- These novel therapies are generally well-tolerated and represent promising treatment options for hypercholesterolemia and CVD.
- Long-term safety data will further solidify their role in managing cardiovascular risk.
Introduction:
Statins reduce low-density lipoprotein cholesterol (LDL-C) and are currently the mainstay in the treatment of hyperlipidaemia and subsequently the prevention of atherosclerotic cardiovascular disease (CVD). Nevertheless, there is a need to further lower LDL-C, especially in subjects with severe forms of hypercholesterolaemia despite maximum doses of conventional drugs and/or in those intolerant to existing therapies.
Areas Covered:
Emerging therapeutic approaches to lowering LDL-C involve blocking LDL-receptor degradation by serum proprotein convertase subtilisin kexin 9 (PCSK9). Human monoclonal antibodies that target PCSK9 and its interaction with the LDL-receptor (AMG145, REGN727 and RN316) have been tested in Phase I - III clinical trials for the treatment of hyperlipidaemia in patients at high CVD risk.
Expert Opinion:
These new agents are administered subcutaneously and have been shown to have major LDL-C and apoB lowering effects either alone or in combination with statins. These novel agents are generally well tolerated and once long-term safety data are available they appear promising therapeutic platforms for the treatment of patients with hypercholesterolaemia at risk for or with CVD not controlled by conventional therapies.
More Related Videos
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:24Glucagon-like Receptor Agonists
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
01:23Dipeptidyl Peptidase 4 Inhibitors
01:29Pharmacogenomics: Identification of New Drug Targets
01:06Lipid Digestion
01:25Lipid Catabolism