Research carried out by Icelandic biotech firm deCODE Genetics suggests that a drug treatment could counter the effects of gene variations that double the risk of heart attack and stroke. Last year, the Reykjavik-based company reported that two versions of a gene called ALOX5AP are linked to an increased risk of both conditions. Now, the researchers have shown that an existing drug, known as DG-031, could reduce this risk in people who inherit the variants. The results of the preliminary trial, published in the Journal of the American Medical Association, show that the drug is safe and reduces the levels of 'biomarkers' associated with heart attack.
It has long been known that people with a family history of coronary artery disease are at increased risk of having a heart attack, although factors such as diet, diabetes and smoking also play an important role. Heart attacks and strokes are both associated with atherosclerosis (a build-up of fatty deposits that cause thickening of the artery walls), a condition which increases the risk of blood clots blocking the arteries that supply the heart or brain.
The ALOX5AP gene makes a protein called 5-lipoxygenase activating protein (FLAP), which is involved in making substances that trigger inflammation in the body. Research suggests that inflammation, the body's response to injury, may play an important role in triggering heart attacks and strokes, since blood clotting forms part of this response. The drug DG031 blocks FLAP activity, so the deCODE team investigated whether it could be used to tackle inflammation, thus lowering the risk of blood clots.
The trial included 268 heart attack patients, most of whom had an at-risk ALOX5AP variant, although some had a variant of another gene involved in inflammation (leukotriene A4 hydrolase). Doctors treated the participants alternately with different doses of DG-031 or a placebo, for a four week period. They found that the drug reduced the blood levels of several proteins involved in inflammation, and did not have any serious side effects. The researchers are now planning another trial, set to begin this autumn, to see if the drug's ability to lower levels of these biomarkers will translate into a reduced risk of heart attack. The new trial will last 18 months and will include around 2,500 patients.
An accompanying commentary by Christopher O'Donnell, of Harvard Medical School, praised the study, but cautioned that because the results are based on biomarkers rather than 'hard clinical end points', it should be viewed as preliminary. He added that the trial 'provides an exciting attempt to translate genetic findings to clinical applications', but that how close doctors are to genome-based diagnostics and therapeutics for heart attack and stroke remains 'uncertain'.
Iceland is thought to have a genetically-distinct population, one of the reasons why deCODE decided to set up a national genetic database to track down disease genes. But critics of its approach have said that common genetic variations linked to illnesses in Icelanders may be rare in other populations. Last year's study showed that two different versions of the ALOX5AP gene are linked to an increased risk of heart attack and stroke in the Icelandic and UK populations.