Course of injections in childhood might help protect people from heart disease later in life

Dec 26 2004

A course of injections in childhood might help protect people from heart disease later in life. And for those whose arteries are already clogged up, a dose of antibodies could provide immediate benefits. That's the enticing vision raised by animal studies.

"It is an extremely attractive idea," says heart expert Andrew Newby at Bristol Royal Infirmary in the UK, who chaired a session of the European Vascular Genomics Network meeting in Cambridge last week where the vaccine research was presented. "In principle it would be a relatively short-term treatment, but give lifetime protection," he says.

Coronary heart disease is the world's leading cause of death, claiming more than 7 million victims annually. Genetic factors play a part, but lifestyle choices such as smoking and a high-fat diet are also important. Most heart attacks are caused by blood clots in the heart's arteries that cut off the blood supply to the organ's muscles.

The trigger is often the rupture of fatty plaques lining the heart arteries, which releases what Göran Hansson at the Karolinska Institute in Stockholm, Sweden, describes as a "dangerous gruel" of phospholipids and proteins that stick to blood platelets, causing a clot.

Many groups worldwide are working on ways to prevent the formation of these plaques, or atherosclerosis. The process involves a complex interaction between the immune system and low-density lipoprotein (LDL), which carries cholesterol in the blood.

About 10 years ago, Jan Nilsson at Lund University in Sweden tried to provoke this immune response by giving oxidised LDL to mice. Oxidised LDL is the main form of the protein found in plaques, so Nilsson expected to see more atherosclerosis. But he was wrong. "To our surprise the mice were protected," he says.

This started him thinking that patients could be vaccinated against atherosclerosis, an idea that his group and Hansson's group have been working on independently. Both teams are using fragments of the oxidised form of LDL to prime the immune system to attack plaques when they first begin to form.

To test the idea, they have been injecting groups of mice with LDL fragments or a saline control. The mice given the LDL vaccination show as much as a 70 per cent reduction in the number of plaques, and existing plaques appeared to stop growing, Nilsson and Hansson reported at the Cambridge meeting. There were no signs of any ill effects.

Nilsson has gone further by exploring whether injecting antibodies to LDL fragments, rather than waiting for the body to produce them after vaccination, also works. Initial experiments in mice suggest they are almost as effective in the short term as the vaccination.

To develop the idea further, Nilsson has teamed up with the Swedish company Bioinvent. Nilsson and Hansson hope initial trials on human volunteers could begin within two years. But nobody yet understands the mechanisms involved, or if the approach will work in humans.