A drug developed to combat cancer and which is currently in the final stages of clinical trials to confirm its safety and effectiveness could also be useful for treating a wide variety of inflammatory diseases, including gout, heart failure, cardiac, cardiomyopathy and atrial fibrillation.
This is the conclusion reached by a team of scientists from the University of Cambridge in a new study in which they have identified a molecule that plays a key role in triggering inflammation in response to substances present in the body that are considered potentially harmful. The findings have been published in the Journal of Clinical Investigation.
Researchers have explained that people are born with a defense system known as innate immunity, which acts as the first line of defense against pathogens in the body. Some of these agents come from outside, such as bacterial or viral infections, while others can occur inside the body.
“We could see new treatments for gout and inflammatory heart disease, as well as other inflammatory conditions, in the not-too-distant future.”
This innate immunity triggers an inflammatory response to attack and eliminate the perceived threat, but sometimes this response becomes overactive and causes damage to the body. An example of this is gout, which occurs when uric acid crystals build up in the joints, causing excessive inflammation and severe pain. Another example is what happens during a heart attack, in which dead cells accumulate in the damaged heart: the body then finds itself under attack and an overly aggressive immune system counterattacks, causing collateral damage to the heart.
A medication that prevents an uncontrolled inflammatory response
Several of these pathologies are characterized by the overactivation of a component of the innate immune response known as an inflammasome, specifically the NLRP3 inflammasome. Scientists at the Victor Phillip Dahdaleh Heart and Lung Research Institute in Cambridge have found a molecule that helps respond to NLRP3. This molecule is known as PLK1 and is involved in a number of processes inside the body, including helping to organize small components of our cells known as microtubules and cytoskeletons. These behave like train tracks within the cell, allowing important materials to be transported from one part of the cell to another.
Dr Xuan Li, from the Department of Medicine at the University of Cambridge and lead author of the study, said: “If we can get in the way of the microtubules as they try to organize themselves, then we can actually slow down the inflammatory response by preventing them. cause collateral damage to the body. “We believe this could be important in preventing a number of common diseases that can cause pain and disability and, in some cases, can lead to life-threatening complications.”
PLK1 plays another important role in the body that may be the key to developing new treatments for inflammatory diseases, since it participates in cell division or mitosis, a process that if not developed properly can cause uncontrolled cell division and the appearance of tumors. For this reason, pharmaceutical companies have decided to test drugs that inhibit its activity as possible cancer treatments.
When Cambridge scientists treated mice that had developed inflammatory diseases with a PLK1 inhibitor, they showed that it prevented the uncontrolled inflammatory response, and at a dose much lower than that needed to treat cancer; That is, inhibiting the molecule “calmed” NLRP3 in non-dividing cells, preventing the overly aggressive inflammatory response seen in these conditions.
The researchers’ next goal is to test its use against inflammatory diseases in clinical trials. “These drugs have already gone through cancer safety trials (and at higher doses than we think we would need), so we are optimistic that we can minimize delays in meeting clinical and regulatory milestones.” said Dr. Li. “If we find that the drug is effective for these conditions, we could see new treatments for gout and inflammatory heart disease, as well as other inflammatory conditions, in the not-too-distant future.”
