Amazing! A new vaccine can significantly reduce low-density lipoprotein (LDL) cholesterol (the bad one) in both mice and rhesus macaque monkeys. The study comes from some researchers led by Dr. Bryce Chackerian of the Department of Molecular Genetics and Microbiology at the University of New Mexic and has been published in the scientific journal Vaccine. The researches created a bacteriophage virus-like particle (VLP) vaccine that produces strong antibody responses against a cholesterol-regulating protein in the blood called PCSK9 (proprotein convertase subtilisin/kexin type 9) which works by binding to the LDL cholesterol receptor in the blood. When the vaccine blocks PCSK9 the LDL receptor can works more effectively and so removes the LDL cholesterol from the blood.
Cardiovascular disease is a leading cause of death in developed nations. The most effective intervention for reducing cardiovascular risk is lowering low-density lipoprotein cholesterol (LDL-C) to normal levels. The lower the better say all the guidelines on hypercolesterolemia from 10 years up till now because today a lot of controlled Clinical trials have demonstrated that elevated levels of the lipoproteins, other than HDL (termed non-HDL cholesterol), particularly LDL-cholesterol, are associated with an increased risk of atherosclerosis and coronary heart disease. Nowadays to lower cholesterol we use mainly statins. These drugs are very efficient but do not work with the same strenght (with a reductions of up to 55% depending on the dose). Others available nonstatin lipid-lowering therapies have limited efficacy, with bile acid resins, nicotinic acid, and fibrates decreasing LDL-C by 10% to 20% on average and ezetimibe-lowering LDL-C by 15% to 20% on average. All these drugs may cause severe side effects, including muscle pain, liver damage, digestive problems, flushing, and increased diabetes risk. Furthermore patients may have more challenging forms of dyslipidemia, such familial hypercholesterolemia that are less sensible to these drugs. Therefore, considerable interest exists in the development of nonstatin therapies that more effectively reduce LDL-C and other atherogenic lipid parameters in high-risk patients on maximally tolerated doses of statin therapy and for those who are statin intolerant.
Recent interest has focused on proprotein convertase subtilisin/kexin type 9 (PCSK9) as a possible therapeutic target. Alirocumab (Praluent, by Sanofi Aventis and Regeneron Pharmaceuticals ), evolocumab (Repatha, by Amgen), and bococizumab (currently in phase III trials, by Pfizer) are three fully human monoclonal antibody to PCSK9. They have demonstrated significant reductions in LDL-C, non–high-density lipoprotein cholesterol (non–HDL-C), apolipoprotein B, and lipoprotein (a) when administered in clinical trials to patients with hypercholesterolemia despite statin therapy. Two of them have already been approved by FDA for lowering LDL cholesterol, but their price (about $14-15000 per year) has caused some controversy. Furthermore since hypercolesterolemia is often a genetic disease as soon as these drugs are suspended high cholesterol is back again and finally do not forget that they are drugs.
The vaccine could be a real rivolution. In fact it has proven to be very effective in mice and macaques, and the researchers are now looking for commercial partners to take it forward to men. But many companies have spent and earn billions of dollars with drugs. The use of VLP-based vaccines targeting PCSK9 peptide could serve as a cost-effective alternative to other therapies and could lead to a widely applicable vaccine-based approach for controlling hypercholesteremia (high cholesterol) and cardiovascular disease. Infact the reserarchers said “If successful, this approach could obviously have a major impact on human health worldwide.”
We will closely follow this story!!
by Guido Francesco Guida