A Canadian study has potentially identified a new and effective therapy for combatting a particularly severe form of inflammatory arthritis.
Researchers from the Schroeder Arthritis Institute, part of the University Health Network (UHN) in Toronto, have made a groundbreaking discovery that may help design treatments for axial spondyloarthritis (SpA), a painful and devastating type of inflammatory arthritis. SpA affects millions of people worldwide, causing inflammation in the spine, eyes, joints, gut, and skin.
The research findings are published in the journal Science Translational Medicine.
Dr Nigil Haroon, a rheumatologist, Co-Director of the spondylitis program and senior author of the study, said: “We currently have very few therapeutic options for the majority of patients living with SpA, and this is a devastating disease that directly impacts quality of life.”
“Although several treatments including biologic drugs have been approved for SpA, 40-50 % of patients do not respond to any treatments and develop severe pain and abnormal new bone formation,” said Dr Akihiro Nakamura, first author on the paper and a spondylitis fellow and PhD candidate in Dr Haroon’s lab. “So, there is a desperate need to find new treatments that are effective and cover all of the clinical symptoms of SpA.”
The mechanisms behind inflammatory arthritis
The team focused their research on the macrophage migration inhibitory factor (MIF), which works as a protein that causes an inflammatory or immune response in the body. This unique study is the first of its kind, as until now, the impacts of MIF on the development of inflammatory arthritis were unknown.
The researchers analysed the expression of MIF and its related receptor – CD74 – finding that they are increased in the blood and tissue of pre-clinical models. Additionally, they discovered that a type of white blood cell that induces an immune response, called neutrophils, secreted higher MIF concentrations in SpA patients than in healthy individuals, which further exacerbates inflammation.
Dr Haroon said: “What this means is that if the body has been exposed to a trigger, too much MIF could be produced in susceptible individuals that could then lead to a diagnosis of SpA later in life. If we can block the excess production of MIF early, we may be able to induce disease remission and prevent disability and mortality linked to SpA.”
A previous study in 2017 illuminated that the concentration or expression of MIF was substantially higher in the blood, joint fluids, and gut tissues of SpA patients in comparison to individuals with different forms of inflammatory arthritis or healthy volunteers. They also identified that MIF is potentially involved in promoting the development of new bone formation.
The study elucidated that the blocker of MIF – MIF096 – is proficient at preventing and mitigating the development of SpA in pre-clinical models, with the team now performing investigations to test other therapies for targeting MIF, potentially leading to a novel treatment for the devastating form of inflammatory arthritis.
The Schroeder Arthritis Institute experts are now looking to analyse the efficacy of MIF blockers in SpA patients in clinical trials to determine the optimal concentration and administration frequency of MIF-targeted drugs in humans and to pinpoint any side effects.
“Patients with SpA experience inflammation, pain, stiffness and over time, this can lead to spinal fusion and loss of mobility. But it’s not just the disease itself that these patients have to worry about,” explained Dr Haroon. “Compared to the general population, there is also a 60% increased chance of stroke, and a 30% increase that they may experience a cardiovascular event or a mental illness.
“The drugs we have currently don’t work for half of all SpA patients. 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.”