Aortic aneurysm – the dilation of the aorta – is a serious condition that lacks effective drug treatment. Researchers at Karolinska Institutet report in the journal PNAS, however, that a common asthma drug can retard the development of aortic aneurysm in mice.
“Our results are exciting and open the way for a medical treatment of this serious vascular disease,” says Professor Jesper Z. Haeggström at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics.
An aortic aneurysm occurs when the wall of the body’s largest artery, the aorta, weakens and swells. The disease progresses slowly and affects some 5 per cent of men and 1 per cent of women over the age of 60. The condition is largely symptom-free and is normally therefore not discovered until late in its development when it threatens to rupture and cause life-threatening haemorrhaging. There are currently no drugs for preventing and treating aortic aneurysm.
In earlier studies, the research group found high levels of particular inflammatory signal substances called leukotrienes in the vascular walls of patients operated on for aortic aneurysm. Leukotrienes drive inflammation and are known for their potential to cause asthma. Since the asthma drug montelukast blocks leukotrienes, the team decided to examine whether it could also have an effect on aortic aneurysm.
Very few side-effects
Their studies on mice revealed that the treatment did indeed reduce the swelling of the aorta and reduced levels of an enzyme that can break down the vascular wall and a protein involved in inflammatory processes.
“This study is particularly interesting from a therapeutic perspective since montelukast is a safe drug with very few side-effects, which means it can be taken over a long period of time,” explains Professor Haeggström. “In the study we used drug doses equivalent to those used in the treatment of asthma patients.”
The researchers hope to be able to start a controlled clinical trial to test the drug’s efficacy on patients with aortic aneurysm.
The study was conducted with researchers at Linköping University and the Technical University of Munich, Germany and financed by the Swedish Research Council, Stockholm County Council, the Novo Nordisk Foundation, the Heart and Lung Foundation, the Ragnar Söderberg Foundation, Karolinska Institutet and the European Research Council (ERC).
Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm
Antonio Di Gennaro, Ana Araujo, Albert Busch, Hong Jin, Dick Wågsäter, Emina Vorkapic, Kenneth Caidahl, Per Eriksson, Bengt Samuelsson, Lars Maegdefessel, Jesper Z. Haeggström
PNAS, online 5 February 2018, doi: 10.1073/pnas.1717906115.