The same mechanism, which could be targeted with existing drugs, would also be involved in inflammatory diseases that affect the spine, liver and arteries.
“I think it’s very important from the point of view of understanding the disease,” said Dr. Robert Battat, of the department of gastroenterology at the University of Montreal Hospital Center. This is a factor that was not appreciated before by the scientific community. And not just in the world of inflammatory bowel disease, but inflammatory immune disease in general.”
The two most common inflammatory bowel diseases are Crohn’s disease and ulcerative colitis, which together are estimated to affect some seven million people worldwide.
These disorders occur when the immune system attacks the intestine by mistake, leading to symptoms that seriously undermine patients’ quality of life. Treatments range from steroids to surgery.
The cure or significant improvement rates for these diseases are around 30% or 40%, said Dr. Talat Bessissow, of the department of gastroenterology at the McGill University Health Center. This means that doctors, using current molecules, are unable to cure more than half of their patients.
Through various experiments and discoveries, researchers at the Frank Crick Institute in London determined that the ETS2 gene is essential for the immune behavior of macrophages (a component of the immune system) and their ability to damage the intestine in the framework of ITNs.
“By systematically characterizing the effects of ETS2 disruption and overexpression in human macrophages, we identify an essential role in inflammation, delineate the mechanisms involved, and show how ETS2 can induce pathogenic macrophage phenotypes,” write the authors. authors in the prestigious scientific journal Nature.
“They identified this gene which still seems to be significantly increased in patients with inflammatory diseases,” added Dr. Bessissow. It increases inflammation by activating macrophages.”
No drugs directly target the ETS2 gene, but cancer drugs called ‘MEK inhibitors’ have been shown in the laboratory to dampen its activity, leading to reduced inflammation.
Researchers are now trying to modify this drug so that it targets only macrophages.
“We do not know what the effect of the proposed solutions will be on humans,” emphasized Dr. Battat, who recalls that it is only in the last ten years that progress has been made in the treatment of these diseases. We don’t have that data.”
All the more so, he continues, as MEK inhibitors cause side effects that would make their long-term use in patients with chronic illness unthinkable.
It now remains to be seen what the real impact of this discovery will be, confirmed Dr. Bessissow. At the very least, researchers now have a very specific target in the treatment of these diseases, which should considerably reduce the “trial and error” approach which remains unavoidable for the moment.
“It’s not going to cure everyone,” he warned. It will perhaps help control the disease and then (…) give patients a good quality of life. But it’s not like when you have an infection, you are given antibiotics and it’s taken care of, you don’t need any more medication. It remains a chronic illness for which we will need long-term treatment.
