June 20, 2017

expert reaction to vaccine to lower cholesterol in mice

Publishing in the European Heart Journal scientists report that the AT04A vaccine induces an effective immune response against the cholesterol-increasing protein PCSK9, in mice.

Dr Tim Chico, Reader in Cardiovascular Medicine & consultant cardiologist, University of Sheffield, said:

“Despite decades of research, treatment for heart disease take only two forms: surgery and other procedures, or regular medication, usually taken daily and lifelong. This experimental animal study takes an alternative inventive approach, immunising mice against a protein that increases cholesterol levels called PCSK9, so that the body’s own immune system switches off PCSK9 leading to a lower cholesterol even weeks after immunisation. As expected, this led to a reduction in cholesterol deposits in the arteries of the mice. If similar effects were achieved in humans it would be likely to lead to a reduction in heart attacks.

“This was a well-conducted but very early study, using animals not humans, and many questions remain about whether this approach could work in man. The theory is sound and I think this might have the potential to replace the need to take regular cholesterol lowering drugs. However, part of the appeal of this approach (that it works long term and possibly permanently) is also a drawback as it might induce side effects that would be difficult to reverse. If a drug causes a side effect this usually disappears when the patient stops the drug, but the approach used in this study would alter the immune system permanently. This would mean that any study in humans would need to assess safety over many years, and it is possible that the effect on cholesterol levels would not be sustained long enough to be of benefit.

“This is yet more proof that cholesterol causes heart disease, and lowering cholesterol reduces risk of heart disease, so it confirms the importance of a healthy lifestyle for everyone and medications such as statins for some people to reduce risk of heart disease.”

* ‘The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol, vascular inflammation, and atherosclerosis in APOE*3Leiden.CETP mice’ by Christine Landlinger et al. published in the European Heart Journal on Tuesday 20 June 2017.

Declared interests

Dr Tim Chico: “I am a committee member and Treasurer of the British Atherosclerosis Society, a charity established in 1999 to promote UK atherosclerosis research.”