Scientists unearth promising therapy target for inflammatory diseases

The process could pave the way for treating diseases like Lupus and sepsis.
Mert Erdemir
Macrophage under microscope

Scientists from Trinity College, Dublin, have discovered a new potential target for treating inflammatory diseases such as lupus and sepsis. The discovery is a significant advancement in comprehending the underlying issues occurring in our bodies during the progression of such diseases.

According to scientists, a key enzyme known as Fumarate Hydratase is suppressed in macrophages, a type of immune cell involved in various diseases such as Lupus, Arthritis, Sepsis, and COVID-19.

"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," said Professor Luke O’Neill, Professor of Biochemistry at Trinity and the lead author of the research article, in the press release.

"We have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases," added joint first-author Christian Peace.

"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."

Promising for developing needed new anti-inflammatory therapies

Scientists unearth promising therapy target for inflammatory diseases
Representational stock image of a Lupus patient.

It was demonstrated in a sepsis model that Fumarate Hydratase was repressed, which is a potentially deadly systemic inflammatory condition that can occur during bacterial and viral infections. Likewise, Fumarate Hydratase was also significantly reduced in blood samples collected from patients with Lupus.

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

The newly-published study is accompanied by another publication by a research group led by Professor Christian Frezza at the University of Cologne and Dr. Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), who has similar 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.

The study paper was published in Nature.

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