4.4 Review

Novel RNAi-Based Therapies for Atherosclerosis

Journal

CURRENT ATHEROSCLEROSIS REPORTS
Volume 23, Issue 8, Pages -

Publisher

CURRENT MEDICINE GROUP
DOI: 10.1007/s11883-021-00938-z

Keywords

Atherosclerosis; Nucleic acid; RNAi; siRNA; Hypercholesterolemia; Hypertriglyceridemia

Funding

  1. Finnish Academy
  2. Leducq Foundation
  3. ERC

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Recent RNAi-based therapies targeting atherosclerosis risk factors, such as blood cholesterol levels, have shown promise in clinical trials, with inclisiran as one of the most advanced treatments approved for hypercholesterolemia. The effectiveness and niche of these new drugs in the cardiovascular disease market will need further evaluation as more patients are treated with them.
Purpose of Review Atherosclerosis, defined by inflammation and accumulation of cholesterol, extracellular matrix, and cell debris into the arteries is a common factor behind cardiovascular diseases (CVD), such as coronary artery disease, peripheral artery disease, and stroke. In this review, we discuss and describe novel RNA interference (RNAi)-based therapies in clinical trials and on the market. Recent Findings The first RNAi-based therapies have entered clinical use for the control of atherosclerosis risk factors, i.e., blood cholesterol levels. The most advanced treatment is silencing of proprotein convertase subtilisin/kexin type 9 (PCSK9) with a drug called inclisiran, which has been approved for the treatment of hypercholesterolemia in late 2020, and results in a robust decrease in plasma cholesterol levels. As the new RNAi therapies for atherosclerosis are now entering markets, the usefulness of these therapies will be further evaluated in larger patient cohorts. Thus, it remains to be seen how fast, effectively and eminently these new drugs consolidate their niche within the cardiovascular disease drug palette.

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