In a groundbreaking study, researchers at the University of Cambridge have identified a promising avenue for treating a wide range of inflammatory diseases, including gout, heart failure, cardiomyopathy, and atrial fibrillation.
Their findings, published in the Journal of Clinical Investigation, reveal a molecule called PLK1 as a key player in triggering inflammation in response to perceived threats within the body.
The Role of Innate Immunity
Our body’s innate immunity serves as the initial defense mechanism against harmful materials, whether they originate externally, like bacterial or viral infections, or internally.
The innate immune response involves triggering inflammation to combat and eliminate potential threats. However, in some cases, this response can become overly active, causing harm to the body.
For instance, gout occurs when urate crystals accumulate in joints, leading to excessive inflammation and severe pain.
Similarly, during a heart attack, the body’s immune system perceives the heart’s damaged cells as a threat, resulting in an aggressive immune response that can cause collateral damage to the heart.
Many of these conditions involve the overactivation of a specific component of the innate immune response known as an inflammasome, particularly the NLRP3 inflammasome.
The researchers at the Victor Phillip Dahdaleh Heart and Lung Research Institute at Cambridge have identified the molecule PLK1, which plays a crucial role in aiding the NLRP3 inflammasome’s response.
The Role of PLK1
PLK1 is involved in various processes within the body, including the organization of microtubules cytoskeletons.
These structures function like train tracks inside cells, facilitating the transportation of essential materials within the cell.
Dr. Xuan Li, the study’s senior author, explains, “If we can disrupt the organization of microtubules, we can effectively slow down the inflammatory response, preventing it from causing harm to the body.
This could be a significant breakthrough in preventing various common diseases that lead to pain, disability, and, in some cases, life-threatening complications.”
But PLK1 also plays a crucial role in cell division (mitosis), which, when disrupted, can lead to uncontrolled cell division and the formation of tumors.
Pharmaceutical companies have been testing PLK1 inhibitors as potential cancer treatments, with one such drug currently in phase three clinical trials.
Potential Treatment for Inflammatory Diseases
When the Cambridge scientists treated mice with inflammatory diseases using a PLK1 inhibitor, they observed that it effectively prevented the excessive inflammatory response.
Importantly, the required dose for this effect was much lower than that used for cancer treatment, indicating the potential for treating inflammatory diseases with minimal side effects.
The researchers are now planning clinical trials to test the use of PLK1 inhibitors for various inflammatory conditions.
These drugs have already undergone safety trials for cancer treatment, which may expedite their development for inflammatory diseases.
Professor James Leiper, Associate Medical Director at the British Heart Foundation, expressed optimism about this research, stating that it offers a promising approach to treat inflammatory heart diseases and other conditions characterized by overactive immune responses.
The study’s findings raise hope for new therapies that could significantly improve the lives of individuals affected by these debilitating diseases.
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The research findings can be found in the Journal of Clinical Investigation.
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