Novel Treatment Target for Inflammatory Diseases

An important breakthrough in understanding what goes wrong in our bodies during the progression of inflammatory diseases has been made by Scientists at Trinity College Dublin's School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute. It has uncovered a potential new therapeutic target in the process.

Understanding Enzymatic Activity in Inflammatory Diseases

The researchers discovered that an enzyme called Fumarate Hydratase is suppressed in macrophages, a type of frontline inflammatory cell linked to a variety of disorders such as Lupus, Arthritis, Sepsis, and COVID-19. Professor Luke O'Neill, Professor of Biochemistry at Trinity, is the principal author of the study. He said, “No one has made a link from Fumarate Hydratase to inflammatory macrophages before and we feel that this process might be targetable to treat debilitating diseases like Lupus, which is a nasty autoimmune disease that damages several parts of the body including the skin, kidneys and joints.”

Fumarate Hydratase Linked with Worsening Inflammation

Joint first-author Christian Peace added, “We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases. We found that when Fumarate Hydratase is repressed, RNA is released from mitochondria which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This process could potentially be targeted therapeutically.”

Fumarate Hydratase was found to be suppressed in a model of sepsis, a potentially fatal systemic inflammatory illness caused by bacterial and viral infections. Similarly, Fumarate Hydratase was significantly reduced in blood samples from Lupus patients.

“Restoring Fumarate Hydratase in these diseases or targeting MDA5 or TLR7, therefore, presents an exciting prospect for badly needed new anti-inflammatory therapies,” said Prof O’Neill.

This newly published work is accompanied by another paper by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr. Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who discovered comparable discoveries in the context of kidney cancer.

“Because the system can go wrong in certain types of cancer, the scope of any potential therapeutic target could be widened beyond inflammation,” added Prof O’Neill.

Source-Medindia