Novel treatment may stop progression of osteoarthritis

Scientists have developed a novel therapeutic treatment that has the potential to stop knee and spine osteoarthritis from progression. The study published in the journal Annals of the Rheumatic Diseases suggests that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in Facial Joint(FJ) and knee osteoarthritis(OA).

Utilizing a variety of experimental models, including animal models and human tissue samples, the scientist from Krembil Research Institute zeroed in on a biomarker, or molecule, called microRNA-181a-5p, which is believed to also cause the inflammation, cartilage destruction, and collagen depletion.

Using a blocker consisting of Locked Nucleic Acid-Antisense Oligonucleotides (LNA-ASO), the team was able to stop the destruction and protect the cartilage.

"The blocker is based on antisense technology. When you inject this blocker into the joints, it blocks the destructive activity caused by microRNA-181-5p and stops cartilage degeneration," said Dr. Akihiro Nakamura, first author of the paper. In addition to testing with animal models, the research team applied this approach using cells and tissues from Toronto Western Hospital patients who have knee and/or spine osteoarthritis.

In addition to greater stability and increased target affinity, in vivo grade LNA-miR ASO are shorter (12–16 nucleotides) in length, compared with other in vitro grade ASO (~20 nucleotides), enabling more efficient cellular uptake via natural mechanisms when administered to animal models in vivo. In vivo grade, LNA-miR ASO can persist for 2–3 weeks in vital organs such as the liver and kidney after systemic injection in mice. This rapid uptake and long retention are features that make these types of oligonucleotides promising for therapeutic use.

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Osteoarthritis (OA) is the most common form of arthritis and a leading cause of chronic pain and disability. Currently, OA drugs only target joint pain, and there are no approved therapies in clinical practice that modify disease progression.

"This is important because there are currently no drugs or treatments available to patients that can stop osteoarthritis," says Dr. Kapoor, co-author of the study. "Current treatments for osteoarthritis address the symptoms, such as pain, but are unable to stop the progression of the disease. "The blocker we've tested is disease modifying. It has the ability to prevent further joint destruction in both knee and spine,” he added.

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“Overall, using two distinct animal OA models in addition to human cells and tissues, we provide the first evidence of cartilage protective effects of LNA-miR-181a-5p ASO. This is the first report showing that LNA-miR-181a-5p ASO attenuates cartilage degeneration during OA across joints (knee and FJ), animal models (rat FJ OA and mouse knee OA models) and species (human, rat, and mouse), write the authors.”

For reference log on to ttp://dx.doi.org/10.1136/annrheumdis-2018-213629