RNA Silencing in the Management of Dyslipidemias

Purpose of Review Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of ‘small-molecule’ hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucle...

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Bibliographic Details
Published in:Current atherosclerosis reports 2021-11, Vol.23 (11), p.69-69, Article 69
Main Authors: Henney, Neil C., Banach, Maciej, Penson, Peter E.
Format: Article
Language:English
Subjects:
Angiology
Anticholesteremic Agents
Cardiology
Cholesterol, LDL
Clinical Trials as Topic
Dyslipidemias - drug therapy
Dyslipidemias - genetics
Humans
Medicine
Medicine & Public Health
Nonstatin Drugs (M. Vrablik
Nonstatin Drugs (M. Vrablik, Section Editor)
Proprotein Convertase 9 - genetics
Proprotein Convertase 9 - metabolism
RNA Interference
Section Editor
Topical Collection on Nonstatin Drugs
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Summary:Purpose of Review Remarkable reductions in cardiovascular morbidity and mortality have been achieved in recent decades through the widespread use of ‘small-molecule’ hypolipidaemic drugs such as statins and ezetimibe. An alternative approach is to perturb the production of proteins through ribonucleic acid (RNA) silencing, leading to long-lasting knock-down of specific biological molecules. This review describes the scientific basis of RNA silencing, and critically evaluates the evidence relating to inclisiran, a small interfering RNA against proprotein convertase subtilisin kexin 9 (PCSK9). Recent Findings Pooled analysis of three recent ORION trials has demonstrated that twice-yearly administration of inclisiran reduces LDL-C by 50% in a range of patient groups, with only mild adverse effects. Summary Inclisiran provides safe, effective and long-lasting reductions in PCSK9 and LDL-C. The results of the phase-3 ORION-4 outcomes study are eagerly awaited. Further promising RNA silencing technologies have the potential to improve the management of dyslipidaemia.
ISSN:1523-3804
1534-6242
DOI:10.1007/s11883-021-00968-7