Arthritis has been one of the most common health conditions in Canada for years, affecting people of all ages with symptoms including joint stiffness and painful inflammation. While there is no known cure, researchers are hoping to find more effective ways to treat and manage arthritis. The Arthritis Society of Canada compiles a list of the top 10 research advances each year, highlighting breakthroughs with promising results. The list for 2020 includes two McGill-led projects supervised by Dr. Hosni Cherif and Dr. Inés Colmegna.
Zombie cells and spinal degradation
Osteoarthritis is one of the most common forms of arthritis worldwide, and is caused by the deterioration of joint cartilage—tissues that cushion the ends of bones. Cherif, a postdoctoral fellow in McGill’s Faculty of Medicine and Health Sciences, led a research project on spinal osteoarthritis.
“My research goal is to understand how intervertebral discs and joints degenerate leading to axial osteoarthritis, and the associated chronic pain,” Cherif wrote in an email to The McGill Tribune.
In particular, Cherif studied the role of senescent cells, often known as “zombie cells,” which permanently stop dividing but continue to age and evade death.
Cytokines, also known as cellular signalling molecules, are typically involved in aiding the immune response at a site of inflammation, but the accumulation of these molecules can cause degradation of the spine.
“[The] accumulation of senescent cells increases cytokine production and inflammation leading to the development of intervertebral disc degeneration,” Cherif wrote.
Cherif’s team identified a synthetic drug, RG-7112, and a natural compound, o-Vanillin, capable of eliminating zombie cells while allowing healthy ones to proliferate. The combination of these molecules has the potential to target inflammation in the spine, thereby reducing the associated chronic pain.
“This will lead to better management or the alleviation of persistent pain to improve the quality of life of patients with osteoarthritis,” Cherif wrote.
Currently, Cherif is expanding his research in drug discovery to treat spinal osteoarthritis by testing out the signalling pathways of other senotherapeutic agents, molecules that specifically target cellular senescence.
“Understanding the mechanism of cellular senescence and disc degradation will facilitate [the] development of novel disease-modifying drugs,” Cherif wrote.
The more the better: High dose vaccine protection
Rheumatoid arthritis (RA) is an autoimmune type of arthritis in which the immune response mistakenly targets host cells, causing joint damage and inflammation. This makes patients more vulnerable to the adverse effects of viruses such as influenza.
Colmegna, an assistant professor working in the Division of Rheumatology at the McGill University Health Centre, led a study focussing on the implications of influenza infections in RA patients.
Specifically, Colmegna studied the effect on antibody production of a standard dose of the influenza vaccine versus a high dose in those with RA. Antibodies are molecular markers that recognize and bind to foreign invaders, signalling their presence to the immune system and initiating an immunological response.
“The findings of our study indicate that compared with the standard dose influenza vaccine, RA patients who receive the high-dose are two to three times more likely to generate ‘protective’ antibodies against the influenza virus,” Colmegna wrote in an email to The McGill Tribune. “This may be associated with a reduced risk of developing influenza.”
By increasing the likelihood of generating more antibodies against influenza, the higher dose increases the effectiveness of the body’s response to infection.
This study is the first of its kind to show that it is possible for those with RA to achieve better protection against influenza by using an existing high dose vaccine.
“Canadian guidelines recommend that RA patients receive an annual standard dose influenza vaccine,” Colmegna wrote. “However, many RA patients do not generate protective antibodies post-vaccination [….] With this approach, a larger number of patients with rheumatoid arthritis might be protected against influenza, a disease that in these patients is associated with significant morbidity and mortality.”
Colmegna hopes that her research findings will increase the availability of high dose vaccines to better protect RA patients against the influenza virus.