Researchers at the University of Toronto in Ontario, Canada have uncovered a new mechanism in the body that may drive the development and progression of axial spondyloarthritis (axSpA).
A pro-inflammatory protein called the macrophage migration inhibitory factor (MIF), and the role it plays in the immune system, was the subject of a study published recently in the journal Science Translational Medicine.1
The findings could lead to new treatments for immune-mediated inflammatory diseases like axSpA.
“The therapeutic options currently available for axial SpA unfortunately do not help a significant proportion of patients living with this condition, and this is a devastating disease that directly impacts quality of life,” said Nigil Haroon, MD, PhD, co-director of the Spondylitis Program at University Health Network in Toronto, a rheumatologist on SAA’s Medical and Scientific Advisory Board, and senior author on the paper.2
In the study, Haroon and colleagues investigated the role of MIF, a substance that induces an inflammatory immune response in the body, and found that the expression of MIF and its receptor were increased in the blood and tissues of mice treated to model axSpA. They also found that human neutrophils (a type of white blood cell) from axSpA patients released higher concentrations of MIF, compared to healthy individuals.1
These findings build on a 2017 MIF study the researchers also published, suggesting that MIF could drive inflammation and new bone formation in axSpA.
Taking their new research a step further, the authors also found that genetic deletion of MIF reduced disease severity in the axSpA-model mice, while transferring MIF-producing neutrophils to healthy mice induced SpA. A small-molecule MIF inhibitor, called MIF-098, successfully suppressed and prevented the onset and development of axSpA.2
The results indicate that MIF is a crucial regulator and a potential treatment target for axSpA, which may lead to the development of new medications down the road.
No major adverse reactions were observed during the mouse study, importantly.3
The researchers are hoping they can next begin clinical trials to test the efficacy of MIF inhibitors in people with axSpA.
Dr. Akihiro Nakamura, a PhD student in the Haroon Lab, was the lead author. “The drugs we have currently don’t work for nearly half of all SpA patients,” Dr. Nakamura said. “At the same time, rates of arthritis are going up worldwide. We believe this treatment could be effective for a good proportion of SpA patients including those who don’t respond to other currently available treatments.”
- Macrophage migration inhibitory factor drives pathology in a mouse model of spondyloarthritis and is associated with human disease (science.org)
- Potential new therapy for inflammatory arthritis | MDLinx
- New spondyloarthritis therapeutic target identified | BioWorld