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Partnership between UHN and company reveals a new putative treatment for spinal arthritis.
Posted On: May 27, 2020
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The spine contains 33 adjacent bones known as vertebrae. Neighbouring vertebrae are connected by facet joints, which can become inflamed and damaged in ankylosing spondylitis.
A UHN study suggests that a novel drug could potentially prevent bone fusion in ankylosing spondylitis (AS), a form of arthritis that affects the spine.
AS is an autoimmune disease characterized by chronic inflammation and damage in the spine joints, which can lead to pain and stiffness in the back. As the disease progresses, AS can cause the bones in spine to fuse, thereby reducing a person’s mobility and quality of life.
“Although there are treatments that can lessen symptoms in AS, none of these treatments have been conclusively shown to prevent spine fusion,” says Dr. Robert Inman, a Senior Scientist at the Krembil Research Institute (UHN).
In the study, a team of researchers led by Dr. Inman characterized NDI-031407, a new drug developed by the company Nimbus Therapeutics. This drug inhibits the activity of TYK2, which is a protein that modulates type III immunity, a branch of the immune system responsible for protecting the body against disease-causing bacteria and fungi. Dysregulation of type III immunity is believed to underpin AS, and genetic studies suggest that TYK2 is also involved.
The researchers showed that NDI-031407 prevented disease progression, by stopping inflammation and joint damage, in two different experimental models of AS. The drug achieved this by dampening the activity of two types of immune cells, Th17 and gamma delta T cells, both of which are key players in type III immunity and are implicated in AS.
“Our study provides compelling evidence that TYK2 modulates the type III immune response and that targeting TYK2 maybe be an effective disease-modifying therapeutic for AS with the potential to not only relieve symptoms but also to prevent bone fusion in the spine,” adds Dr. Inman.
The majority of this work was performed by Dr. Eric Gracey, a former PhD student under Dr. Inman’s supervision. Dr. Gracey is now completing a postdoctoral fellowship in Gent, Belgium, where he is continuing to examine arthritis and help develop new treatments for it.
This work was supported by the Canadian Institutes of Health Research, Nimbus Therapeutics, the Austrian Science Fund and the Toronto General & Western Hospital Foundation.
Gracey E, Hromadová D, Lim M, Qaiyum Z, Zeng M, Yao Y, Srinath A, Baglaenko Y, Yeremenko N, Westlin W, Masse C, Müller M, Strobl B, Miao W, Inman RD. TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis. J Clin Invest. 2020 Apr 1. doi: 10.1172/JCI126567.