Scientists have made an important breakthrough in understanding what goes wrong in our bodies during the progression of inflammatory diseases and – in doing so – unearthed a potential new therapeutic target.

The scientists have found that an enzyme called Fumarate Hydratase is repressed in macrophages, a frontline inflammatory cell type implicated in a range of diseases including Lupus, Arthritis, Sepsis and COVID-19. 

The lead author of the research article that has just been published in leading international journal, Nature 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.” 

Joint first-author 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 shown to be repressed in a model of sepsis, an often-fatal systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased. 

https://www.nature.com/articles/s41586-023-05720-6