Intercepting the Messenger

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Potential new treatment for osteoarthritis could stop knee and spine joint destruction.
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The new drug intercepts and blocks microRNA-181a-5p molecules, just as a defensive team is meant to intercept the ball from an opposing team.
Researchers at the Krembil Research Institute have developed a novel therapeutic treatment that has the potential to stop knee and spine osteoarthritis in its tracks.
The team led by Dr. Mohit Kapoor, UHN Arthritis Research Director and Krembil Senior Scientist, published the results in the Annals of the Rheumatic Diseases, a leading journal for arthritis research.
Osteoarthritis is the most common form of arthritis. It affects about five million Canadians and is characterized by a breakdown of the protective cartilage found in the body’s spine, hand, knee and hip joints.  
“Current treatments for osteoarthritis address symptoms, such as pain, but are unable to stop the progression of the disease,” explains Dr. Kapoor. 
Dr. Kapoor and his team used a variety of experimental models to identify a molecule, called microRNA-181a-5p, which is believed to cause the inflammation, cartilage destruction and collagen depletion associated with the disease. They then developed a drug to selectively prevent microRNA-181a-5p from doing its job.
“When you inject this synthetic drug into the joints, it blocks the destructive activity caused by microRNA-181-5p and stops cartilage degeneration,” says Dr. Akihiro Nakamura, first author of the paper and a postdoctoral research fellow in the Kapoor lab. 
The drug also prevented the breakdown of cartilage tissues in an experimental model using cells taken from Toronto Western Hospital patients with knee and/or spine osteoarthritis.
Next steps for the research team include starting human safety studies that will determine the proper dosage and method for delivering the new drug to inflamed joints. 
This work was supported by the Krembil Foundation, the Canadian Institutes of Health Research and the Toronto General & Western Hospital Foundation.
Nakamura A, Rampersaud YR, Nakamura S, Sharma A, Zeng F, Rossomacha E, Ali SA, Krawetz R, Haroon N, Perruccio AV, Mahomed NN, Gandhi R, Rockel JS, Kapoor M. microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints. Ann Rheum Dis. 2018 Oct 4. pii: annrheumdis-2018-213629. doi: 10.1136/annrheumdis-2018-213629. 

Dr. Mohit Kapoor, Senior Scientist, Krembil Research Institute. Photo courtesy of the Globe and Mail.