A single injection of a drug already used in cancer could re-train the immune system to slow the build-up of fatty plaques in arteries after a heart attack. Heart attacks and strokes kill 19 million people worldwide each year, and cost the European Union’s economy 196 billion euros annually. Current treatments lower cholesterol but do not address the underlying immune-driven inflammation that makes atherosclerosis worse. The researchers have identified a subset of white blood cells that protect arteries rather than inflame them, and they know that low doses of interleukin-2—20 to 100 times lower than the cancer dose—can selectively expand this helpful population. If this trial in patients with a recent acute coronary syndrome shows that low-dose IL-2 safely boosts protective immune cells and dampens harmful inflammation, it could open the door to a completely new class of treatments for cardiovascular disease—one that targets the immune system rather than cholesterol. That would shift how doctors prevent second heart attacks, potentially reducing repeat hospitalisations and long-term disability for millions of patients.
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Cardiovascular diseases (CVD) are the leading cause of mortality in Europe (5 million deaths per year) and in the World (19 million deaths) and strike both low- and middle-income countries as well as affluent countries. CVD cost the European Union's economy 196 billion euros in 2009. CVD mostly result from atherosclerosis, the build-up of fatty plaques in the walls of our arteries, which is the cause of heart attacks and strokes. The accumulation of cholesterol in the arteries leads to subtle chemical modifications making it recognised by our immune system as a strange 'non-self' material. The activated immune system sends white blood cells to try and clear away the fatty material, but this can cause the artery to become inflamed and make the disease worse. More than a decade of research on the mechanisms of atherosclerosis has led to the identification by our group of some types of white blood cells that are helpful and can slow down the disease. Current treatments of atherosclerosis do not target the immune system. Thus, harnessing the helpful white blood cells might give us new effective treatments to combat the build up of fatty plaques in our arteries. A substance called interleukin (IL)-2 is licensed for use at high dose in cancers of the kidney. Interestingly, recent research indicates that low doses of IL-2 (20 to 100-fold lower than the doses used in cancer) selectively stimulate and expand the population of helpful white blood cells. We want to harness this new knowledge for the development of new treatments that stimulate the cells that protect our arteries without stimulating the damaging ones, and re-purpose IL-2 for the treatment of cardiovascular diseases. Here, we will test the hypothesis that treatment of patients with low doses of IL-2 will increase the population of helpful white blood cells to reduce the activation of the harmful ones and limit their detrimental effects on our arteries. We expect this new treatment strategy to have major impact on both the individual and societal levels. The project will be accomplished by a very experienced team of scientists and clinicians, who are world leaders in this field, working in the University of Cambridge, UK, one of the best scientific environment worldwide.
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