US scientists have found that a drug approved by the Food and Drug Administration may help prevent symptoms of genetic heart disease and reduce the progression to heart failure.
Researchers may have found a treatment track to overcome arrhythmogenic right ventricular dysplasia (ARDV). This hereditary heart disease which results in rhythm deficiencies in the ventricles of the heart is largely responsible for sudden deaths in athletes under 35 years of age.
In France, this phenomenon can amount to more than 1,000 deaths per year, in sporting activity or physical leisure activity, according to data from theResearch institute for well-being, medicine and health sport.
In cardio-arterial diseases, heart cells break down over time, and these cells are replaced by damaged and inflamed scar tissue. These scars can increase the risk of irregular heartbeats and lead to sudden cardiac death if the scar tissue stiffens the heart wall and makes it unable to pump.
The role of immune cells
If a person knows they have a genetic mutation that can cause ARVC, doctors instruct him to change his lifestyle, such as limiting his physical activity and taking medications that keep his heart rate low. But no medication exists to treat the underlying structural defects relating to this disease.
The authors of the study, researchers at the Johns Hopkins University School of Medicine (United States), analyzed the role of the immune system using mouse models and human heart muscle cells with ARVD.
Published in the journal Trafficthe study shows that the inflammation associated with the disease was linked to high levels of macrophages, a type of immune cell that can be found around healing cuts or scrapes.
“Macrophages are usually the ‘nice ones’ that help heal an injury and then go away. But in DVDA they permanently take up residence in the heart, which over time reduces its function,” explains Stephen Chelko, who led the study.
Twice as high heart function in mice
Prof. Chelko’s team also found that in ARVD, the heart cells themselves are triggered by a protein called NF-κB, activated to produce chemicals called cytokines, which act as beacons for other inflammatory cells and molecules. .
When researchers treated mice and human stem cells with a drug aimed at blocking the action of NF-κB, the heart cells stopped producing several of these cytokines, which led to a decrease in the infiltration of inflammatory cells. Similar results were seen in mice, which showed twice the heart function.
Although Bay-11-7082 is currently only used in the laboratory for experimental purposes, the United States Food and Drug Administration has approved canakinumab, a drug that targets the same inflammatory pathway, as part of treatments for juvenile arthritis and a series of rare autoinflammatory syndromes.
Canakinumab is also being studied for use in coronary artery disease. Chelko’s group is currently studying whether this drug would have the same effect as Bay-11-7082 in DVDA to prevent long-term heart disease.
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