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Anti-PCSK9 vaccine shows cholesterol-lowering potential in a mouse model

PCSK9 has recently emerged as a promising vaccine target for the effective and economic treatment of hypercholesterolaemia and atherosclerosis.

The newest class of cholesterol-lowering drugs to emerge are proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, such as alirocumab and evolocumab. However, these monoclonal antibodies are expensive and need repeated administration.

In a recent paper, researchers explored the efficacy of a vaccine, called AT04A, designed to trigger production of antibodies against PCSK9 in mouse models of coronary heart disease.

They found that, after 18 weeks, AT04A-vaccinated mice being fed a western-type diet had around 50% lower total cholesterol (−53%, P<0.001) and significantly reduced low-density lipoprotein cholesterol (LDL-C) levels compared with controls. Markers of blood vessel inflammation were also significantly reduced, as well as atherosclerotic lesion areas (−64%, P=0.004).

Reporting in the European Heart Journal[1] (19 June 2017), the researchers say AT04A could be a cost-effective and sustainable approach to lowering LDL-C levels, and it is currently being tested in a phase I clinical trial.

Citation: Clinical Pharmacist DOI: 10.1211/CP.2017.20203111

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Supplementary images

  • 3D structure of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors

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