FRONT PAGES: A Potential New Treatment For Inflammatory Arthritis

dWeb.News Article from Daniel Webster dWeb.News

dWeb.News Article from Daniel Webster dWeb.News

Newsswise — TORONTO — Researchers at the Schroeder Arthritis Institute (UHN), in Toronto have published a paper that suggests new therapies for axial spondyloarthritis. This debilitating and painful form of arthritis affects around 1-2% of Canadians. It causes inflammation in the spine and joints. We currently have very few treatment options for patients with SpA. This is a debilitating disease that directly affects quality of life.” Dr. Nigil Haroon (a rheumatologist and Co-Director at the spondylitis programme and senior author of the paper) says.

“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,” says 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 study focuses on the role of the Macrophage migration inhibitory factor (MIF), which functions as a protein that induces an inflammatory or immune response in the body. The role of MIF in SpA’s disease progression was not known until now.

In this study, researchers observed that the expression of MIF and its receptor CD74, is increased in the blood and tissues of pre-clinical models. Researchers also discovered that SpA patients secreted more MIF than healthy individuals. This causes other cells to produce more inflammation.

“This means that, if the body is exposed to a trigger, excessive MIF may be produced. This could lead to an earlier diagnosis of SpA. Dr. Haroon explains that if we can stop the excessive production of MIF earlier, we might be able induce disease remission. This will prevent disability and death linked to SpA. Haroon.

In a 2017 paper, the researchers found that the concentration or expression of MIF is substantially increased in the blood, joint fluids and gut tissues of SpA patients, compared to those of a different type of arthritis patients or healthy volunteers. They also showed that MIF may be involved in the promotion of bone formation. These new findings have confirmed those results and further enhanced our understanding of MIF’s role in SpA.

The specific blocker of MIF, called MIF098, successfully prevented and restricted the disease onset and development of SpA, in the pre-clinical model. The team will now focus on the potential of other therapies that target MIF. This could help to find a new treatment for SpA.

“Patients with SpA experience inflammation, pain, stiffness and over time, this can lead to spinal fusion and loss of mobility. These patients need to be concerned about more than the disease. Dr. Haroon says that there are also increased chances of stroke and a % increase in the likelihood of a cardiovascular event or mental illness. “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.”

For Dr. Nakamura, a clinician from Japan who came to the Schroeder Arthritis Institute to become a leading researcher in the area of inflammatory arthritis, these new findings are nothing short of ‘exciting.’

“In research, once we make a new discovery, that has the potential to help many more patients than I could in my clinic, back in Japan,” says Dr. Nakamura. “So that motivates me a lot.”

Researchers are next hoping to test the efficacy of MIF blockers in patients with SpA through clinical trials, where they would look to determine the optimal concentration and administration frequency of MIF-targeted drugs for humans, as well as study potential side effects, to ensure safety.

” The drugs currently available don’t work in half of SpA patients,” Dr. Haroon says. “At the exact same time, arthritis rates are increasing 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.”

Competing Interests

Dr. Nigil Haroon acts as a consultant for Abbvie, Eli Lilly, Janssen, Novartis and UCB, none of whom have funded this study.

This work is supported by the Canadian Institute of Health Research, Arthritis Society, Krembil Foundation, UHN Foundation, American College of Rheumatology (ACR) Research Fund, National Institutes of Health (NIH), Natural Sciences Research Council, Canada Foundation for Innovation (CFI), Ontario Research Fund, IBM, Ian Lawson van Toch Fund, Medicine by Design Program, MiTACS Accelerate Fellowship, Spondyloarthritis Research and Treatment Network (SPARTAN), and Spondyloarthritis Research Consortium of Canada (SPARCC).

About the Schroeder Arthritis Institute

The Schroeder Arthritis Institute is the largest multidisciplinary arthritis hub in Canada, integrating medical, surgical and basic science aspects of Hand, Orthopaedics, Osteoporosis and Rheumatology, with a goal of making a global impact in discovery, learning and patient care. The Institute comprises 51 scientists and clinician-scientists, 113 trainees and 200 staff. Toronto Western Hospital is the home of The Schroeder Arthritis Institute. For more information, visit: https://www.uhn.ca/arthritis

About University Health Network

University Health Network consists of Toronto General and Toronto Western Hospitals, the Princess Margaret Cancer Centre, Toronto Rehabilitation Institute, and The Michener Institute of Education at UHN. University Health Network is a leading source of education, research and patient care. It is home to the largest hospital-based research program of Canada. This includes major research in cancer, arthritis, neurology, transplantation and neurosciences. University Health Network is an affiliated hospital. For more information, visit: www.uhn.ca

MEDIA CONTACT

Heather Sherman, Senior Advisor, Public Affairs

Neuroscience | Arthritis | Vision

University Health Network | 437-240-5723 | [email protected]

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