Arthritis Centres are the rheumatology divisions of the departments of medicine in Canadian universities, including accredited pediatric rheumatology centres.

For over 30 years, the Arthritis Society has provided annual funding to Arthritis Centres across Canada. As centres of clinical expertise, research, and education, their role in the Canadian healthcare environment is to help ensure that more Canadians with arthritis receive better care.

Recipients of up to $15,000 for a term of one year (2018/19) are:

• BC Children’s Hospital, University of British Columbia
• CHU de Quebec, Université Laval
• QEII Health Science Centre, Dalhousie University
• McMaster University
• McMaster Children’s Hospital, McMaster University
• St. Joseph’s Health Centre, Western Ontario
• SickKids Hospital, University of Toronto
• Montreal Children’s Hospital, McGill University
• University of Manitoba
• University of Calgary
• University of Alberta

Arthritis Centre grants support centres that align with one of the Arthritis Society’s primary areas of focus – to build and support of pipeline of strong researchers. Proposal objectives support capacity building programs with an aim to increase the number of academic rheumatologists in Canada and/or to support research training in rheumatology.

Project title: A mouse model to design therapies targeting TRAF1 in rheumatoid arthritis

Annual commitment:
Year 1: $125,000
Year 2: $125,000
Year 3: $125,000

Project summary: Learning how to put the brakes on rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory disease where the body’s immune system starts to attack the lining of the joints. Understanding more about how the body usually keeps inflammation in check, and how this goes wrong in RA, can help researchers design new treatments. Dr. Ali Abdul Sater is launching his arthritis research career by studying a protein that acts as a “brake” on inflammation, which may be a good target for future RA therapies. By developing a new, unique mouse model to study in the lab, Dr. Abdul Sater will discover how this protein can be manipulated to effectively treat RA. New RA treatments could improve health outcomes and give patients more options.

Project title: Genetics of manifestations and complications of systemic lupus erythematosus

Annual commitment:
Year 1: $125,000
Year 2: $125,000
Year 3: $125,000

Project summary: Leading the way in genetic studies of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a life-threatening inflammatory disease for which there is no cure. About 1 in 5 of those diagnosed with SLE are children or adolescents, who have a higher risk of suffering from disease complications and treatment side effects. Genetic differences have important effects on who gets SLE, how it manifests, and what complications arise. Dr. Linda Hiraki is launching her research career by leading a coordinated effort to study how genetic changes (especially rare ones) affect SLE and its complications in children and adults across North America. This knowledge will lead to improved care and enable the discovery of new treatments.

Project title: Advanced multimodal imaging to predict early inflammatory arthritis progression

Annual commitment:
Year 1: $124,960
Year 2: $124,660
Year 3: $124,910

Project summary: A triple threat for imaging joint damage in rheumatoid arthritis

People with rheumatoid arthritis (RA) experience swelling and bone damage in their joints, but how damage starts and gets worse is unclear. Launching her career in arthritis research, Dr. Sarah Manske is using specialized medical imaging to understand how joint swelling and bone changes are connected. Magnetic resonance imaging (MRI) and ultrasound are very good for looking at the swelling in the soft tissues of the joints. Computed tomography (CT) is very good for looking at the bones. By combining all three types of imaging, Dr. Manske will follow how joint damage happens in the hands of people with RA. This research will help guide more effective treatment strategies to minimize joint damage.

Project title: Establishing the validity of quality of life measures in young children with juvenile idiopathic arthritis

Annual commitment:
Year 1: $102,794
Year 2: $119,705
Year 3: $101,540

Project summary: Quality of life in childhood arthritis: How do we measure up?

Understanding the impact of childhood arthritis on quality of life, and how this changes with treatment, is a crucial factor for considering how to make the most of limited healthcare resources and improving childhood arthritis care in Canada. Current methods for measuring quality of life have not been tested in children with arthritis, or in children under eight years old. Dr. Susanne Benseler is collecting quality of life data from the families of young children with arthritis using a survey tool to test if this approach captures the pain of childhood arthritis and its impacts on life in a meaningful way. This will improve how quality of life is measured in children with arthritis, providing an approach that could become the standard in research and clinical practice.

Project title: Randomized controlled trial of staged versus simultaneous bilateral knee arthroplasty

Annual commitment:
Year 1: $119,940
Year 2: $118,120
Year 3: $120,000

Project summary: Replacing both knees due to severe osteoarthritis: One at a time, or both together?

For some people with osteoarthritis (OA), joint replacements are the only option to relieve the pain and restore function. When both knees need to be replaced, it’s not yet clear whether it’s better for the patient to replace them both at the same time in one operation, or stage the two replacements a few months apart. Both approaches have pros and cons with respect to how the patient recovers from surgery. Dr. Eric Bohm is leading a clinical trial across Canada to compare the two approaches in terms of recovery times, pain relief, joint function, patient satisfaction, and time off work. The results will be used to help patients make informed choices about what surgical approach is best for them.

Project title: Mapping the epidemiology and the role of treatments in mental health complications in inflammatory arthritis (MATTERS)

Annual commitment:
Year 1: $65,073
Year 2: $57,125
Year 3: $84,748

Project summary: Mental health matters in arthritis

The physical effects of arthritis are undeniable and devastating. However, arthritis also has a complex relationship with mental health. Having arthritis may lead to depression or anxiety, and in turn, depression and anxiety can worsen arthritis. Dr. Mary De Vera is using “big data” (e.g., many records of doctors’ visits, hospitalizations, and prescriptions) to study whether the burden of depression and anxiety in British Columbians with arthritis is increasing over time and the effect of other contributing factors, such as medication use. This will be the first study of its kind in Canada on mental health in arthritis. It will not only help improve the lives of people with arthritis but will also bring more awareness to this important matter.

Project title: The Ondansetron Premedication Trial in Juvenile Idiopathic Arthritis (OPT-JIA)

Annual commitment:
Year 1: $120,000
Year 2: $102,400
Year 3: $97,936

Project summary: A clinical trial to prevent side effects of treatment in children with arthritis

Many children with arthritis are treated with methotrexate, a drug commonly used in chemotherapy that also effectively controls joint swelling. While this drug has major benefits, too many children with arthritis have nausea and vomiting as a side effect. This can impact every facet of life for children and their families, so many children switch to treatment with expensive biologics, even if methotrexate was working. Dr. Jaime Guzman is leading a clinical trial to see if a drug called ondansetron can prevent nausea and vomiting in children with arthritis starting methotrexate, allowing them to continue methotrexate treatment if it is effective. If successful, this trial could influence clinical practice to improve quality of life for children with arthritis and their families.

Project title: Proof-of-concept study of an electronic medical record (EMR) reminder intervention to optimize the primary and secondary prevention of comorbidities in people with inflammatory arthritis

Annual commitment:
Year 1: $120,000
Year 2: $120,000
Year 3: $120,000

Project summary: Empowering doctors to prevent chronic health problems in people with inflammatory arthritis

The inflammation that causes joint pain in inflammatory arthritis (IA) may also put people at risk for other chronic health problems such as heart disease, diabetes, osteoporosis, infections, and some cancers. These serious co-existing health conditions can compromise quality of life and even lead to early death. Dr. Diane Lacaille is developing and testing an automated way to send family doctors timely reminders to check for and manage risk factors for chronic diseases in their patients who have IA. This will help them establish effective prevention strategies to keep people with IA as healthy as possible so they can live long, full lives.

Project title: Identification of mitochondrial antigens targeted by auto-antibodies in systemic lupus erythematosus (SLE)

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Examining the immune reactions in systemic lupus erythematosus

Mitochondria are small structures inside cells that are believed to have evolved from bacteria. If cells are damaged and mitochondria are released outside, the body’s immune system can mistake them for bacteria and mount an immune response as if there was an infection. This immune overreaction takes place in systemic lupus erythematosus (SLE), an autoimmune form of arthritis. Under the supervision of Dr. Éric Boilard, Yann Becker will study how mitochondria are recognized by the immune system in SLE and to identify signs that may help improve SLE diagnosis or predict how it will progress. This could lead to new clinical tests to help ensure that people with SLE receive the best care possible.

Project title: Investigating the therapeutic role of ex vivo polarized monocytes/macrophages in osteoarthritis

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500

Project summary: Using a person’s own immune cells as a therapy for osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, affecting millions of Canadians. While there are several strategies to manage the pain and other symptoms of OA, there is no cure and advanced disease can require surgical joint replacement. Under the supervision of Dr. Sowmya Viswanathan, Mable Wing Yan Chan is investigating an innovative new approach to OA therapy – using the body’s own immune cells. This study will test whether immune cells can be taken out of the blood and “trained” in the lab to reduce inflammation and joint damage, before being injected back into human joint tissues. This research could lead to a completely new, personalized approach to OA treatment.

Project title: Cost-effectiveness of early and aggressive treatment for children with juvenile idiopathic arthritis including the spillover effects on quality of life and productivity of children and their parents

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Understanding the costs of childhood arthritis – for the whole family

Arthritis can affect people at any age, including children. While the development of new therapies for childhood arthritis has made a tremendous difference to affected children and their families, new medications are expensive, and all have risks as well as benefits. Under the supervision of Dr. Deborah Marshall, Luiza Grazziotin is studying the impact that early treatment of childhood arthritis has on parents’ quality of life and their family’s financial well-being. This broader understanding of the burden of childhood arthritis on families may help inform drug reimbursement decisions to support optimal care for children with arthritis across the country.

Project title: Bone marrow lesions and cartilage mechanical properties in osteoarthritis

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Understanding how bone bruises contribute osteoarthritis

“Bone bruises” are areas of damage commonly seen on medical imaging scans of people with osteoarthritis (OA) in the knee or hip. They have been linked to having higher levels of pain, and arthritis that worsens more quickly. However, it is unclear how bone bruises affect the bone are cartilage that lie over them, and the role they play in causing OA. Under the supervision of Dr. David Wilson, Carly Jones is measuring how bone bruises in the knee and hip joints affect the stiffness of nearby bone and cartilage to understand how they contribute to the pain and joint damage of OA. This information is essential to developing more effective ways to treat, slow, or stop the disease.

Project title: Beyond training: understanding patient/public experience of power dynamics as engaged partners in arthritis research

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Power dynamics experienced by patient partners in arthritis research

Engaging patients and other members of the public in health research in meaningful ways can ensure that research is informed by patient priorities and designed to have the most potential for impact. The arthritis research community has been a leader on this front, but there are still unanswered questions around how to best integrate these partners within research teams. Under the supervision of Dr. Linda Li and Dr. Laura Nimmon, Graham Macdonald is studying the power dynamics of arthritis research teams from the perspectives of both patient partners and researchers. These insights will help improve patient engagement in research, fostering research that involves and empowers people with arthritis to transform this disease.

Project title: Culture preconditioning strategies to enhance the therapeutic efficacy of adipose tissue-derived mesenchymal stromal cells for the treatment of osteoarthritis

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Harvesting cells from fat to treat osteoarthritis

Osteoarthritis (OA) is the most common form of arthritis, which has a devastating impact on millions of Canadians. New treatment options are needed, because there is no cure and advanced cases may require surgical joint replacement. Under the supervision of Dr. Sowmya Viswanathan and Dr. Rajiv Gandhi, Kevin Robb is studying a new potential therapy that uses cells taken out of fat tissues that interact with the immune system, and injects them into affected joints. He will study how these cells work in detail, how they interact with joint tissues in OA, and whether they can be “trained” in the lab to reduce inflammation, joint damage and pain. This could lead to a new treatment to be tested in clinical trials.

Project title: CD154 and its receptors in rheumatoid arthritis

Annual commitment:
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: Towards a new targeted treatment strategy for rheumatoid arthritis

Rheumatoid arthritis (RA) involves inflammation triggered by many signals in the body, including signals from several proteins in the cell. Many of these signals are the targets of the class of RA drugs known as biologics – complex medications made by living cells. These drugs are expensive and, like all drugs, have side effects as well as benefits. Under the supervision of Dr. Walid Mourad, Suzanne Salti is studying an inflammatory signalling protein involved in RA and how it interacts with several novel protein partners. The goal is to exploit these discoveries to develop a new type of biologic – one that could potentially be less expensive and have fewer side effects.

Project title: Endothelial ephrin B4 and ephrin B2 signalling in tissue fibrosis

Annual commitment (plus 50/50 match):
Year 1: $10,500
Year 2: $10,500
Year 3: $10,500

Project summary: The biology behind a life-threatening complication in scleroderma

Scleroderma is a form of arthritis that involves a build-up of tough scar-like tissue in the skin and sometimes other organs through a process called fibrosis. In the joints, this can lead to stiffness and pain. If it affects the lungs, fibrosis can be life-threatening. Under the supervision of Dr. Mohit Kapoor, Brian Rai-Ling Wu is studying a specific protein involved in lung fibrosis to learn where it comes from and how it works, especially in the context of the cells that line the blood vessels. Pinpointing how this protein leads to lung fibrosis could lead to new treatments for this serious complication of scleroderma.

Project title: More than skin deep: the microbiome of psoriasis and psoriatic arthritis

Annual commitment (plus 50/50 match):
Year 1: $10,500

Project summary: The role of skin bacteria in psoriasis and psoriatic arthritis

Psoriasis is an inflammatory skin disease that can be associated with arthritis in up to 30% of the people who have it. Psoriatic arthritis (PsA) can lead to progressive joint damage, pain, disability, and poor quality of life, but its impact can be quite variable. This variation cannot yet be explained by known risk factors. Under the supervision of Dr. Vinod Chandran, Meital Yerushalmi is working on a first-of-its-kind study of skin bacteria in people with psoriasis and different types of PsA in the context of the person’s genetics. This research will reveal what role skin bacteria play in the development and severity of PsA, which could provide insight into possible new treatments.

Project title: microRNA discovery in early and late knee osteoarthritis using next generation sequencing

Annual commitment (plus 50/50 match):
Year 1: $20,000
Year 2: $20,000

Project summary: Towards a blood test for early detection of knee osteoarthritis

There is a significant gap in the care of people with osteoarthritis (OA) due to challenges in diagnosing it early and a lack of treatment options. Researchers are searching for signs in the blood that could help catch OA earlier. Dr. Shabana Ali is working towards discovering new ways to distinguish groups of people with knee OA based on their personal characteristics (e.g. age, sex, body mass index) and disease severity, using a cutting-edge technology to create “fingerprints” of molecules found in the blood. These results could be used to develop a simple blood test to diagnose early knee OA, which could allow people to begin exercise or physical therapy programs to prevent progression of the disease.

Project title: Role of microRNAs in preclinical rheumatoid arthritis

Annual commitment (plus 50/50 match):
Year 1: $20,000
Year 2: $20,000
Year 3: $20,000

Project summary: Learning more about how rheumatoid arthritis starts in a high-risk population

Rheumatoid arthritis (RA) is an inflammatory condition where body’s immune system attacks its own joints leading to pain and impaired mobility. Molecules that act as “switches” to turn genes on and off misbehave in some people with a high risk of RA, leading to inflammation and eventually the disease. Dr. Vidyanand Anaparti will study these molecules in children from Indigenous communities in Northern Manitoba who have a high risk of developing RA. In doing so, he will learn more about how these molecules work and whether they can help predict who will get RA. This could eventually lead to a blood test to catch RA early in this high-risk population, even before symptoms appear.

Project title: Improving strength training in people with rheumatoid arthritis: a foundational behaviour change science approach

Annual commitment (plus 50/50 match):
Year 1: $20,000
Year 2: $20,000
Year 3: $20,000

Project summary: Strength training for people with rheumatoid arthritis: promising strategies to get active

Current guidelines recommend that people with rheumatoid arthritis (RA) perform strength training exercises at least twice a week to build or maintain muscle, and reduce pain and fatigue. However, remarkably few people with RA meet this goal. This disparity highlights an important missed self-management opportunity. Dr. Jasmin Ma is studying what factors help and hinder participating in strength training among people with RA and will identify the best strategies to support their long-term engagement in this type of physical activity. These results will inform future health promotion efforts to empower people living with RA to improve their quality of life.

The CRA (CIORA)-AS Clinician Investigator Award is intended to provide new clinician investigators, within 5 years of a full time clinical faculty appointment, with what would usually be their first opportunity, upon completion of post graduate training, to demonstrate their ability to initiate and carry out independent research of clear relevance to arthritis, before becoming involved in carrying out the full clinical, teaching and research duties expected of a regular member of the university staff.

Awardees are expected to complete a research project during the term of this salary award. The proposed project must be of clear relevance to rheumatic diseases and be aligned with one or more of the research pillars under the Canadian Initiative for Outcomes in Rheumatology Care (CIORA) grant program.

• Awareness/Advocacy/Education
  1. Health Economics/Sustainability of Health Care/Quality Improvement
• Early Access for rheumatic diseases Patients
• Multi-Disciplinary Care Teams

Please visit the CRA website for the 2018 results.

Assistant Professor, Dept. of Medicine, Schulich School of Medicine & Dentistry, Western University 

Project Title: The dual role of synovial macrophages in post-traumatic and metabolic osteoarthritis.

Annual Commitment:
Year 1: $120,000
Year 2: $120,000
​Year 3: $120,000

Keywords: osteoarthritis, synovitis, articular cartilage, macrophage, inflammation, animal models of OA, early arthritis, flow cytometry, metabolic OA, post-traumatic OA

Project Summary:

• Why?: OA is different from other types of arthritis with high-grade inflammation (e.g. rheumatoid arthritis). OA presents with low-grade, chronic, and often intermittent inflammation. Research has shown that inflammation in the lining of joints from people and animals with OA contains high numbers of immune cells called macrophages.
• What?: This project proposes to answer these questions: 
  1. Are OA macrophages mainly pro-inflammatory or anti-inflammatory, and are they different in early vs. late stages, and in post-traumatic OA vs. metabolic OA?
  2. What are the gene expression profiles of OA macrophages in different stages and types of OA?
  3. Does treatment that specifically causes loss of macrophages reduce or accelerate OA, and does the effect depend on treatment timing or type of OA?
• How?: Use two animal models of post-traumatic OA to examine the knee joint tissues to assess whether the macrophages present in early and late knee OA are mostly pro-inflammatory vs. anti-inflammatory, and whether the macrophages occurring in each type of OA are different.
  
  Use advanced genetic tools to measure the expression of all macrophage genes, which will give us critical insight into how these cells are functioning at different stages of each type of OA.
  
  Use a treatment to selectively remove all macrophages from the rats while OA develops, or after OA has been established.
• Impact?: To help us understand if macrophages worsen or protect against knee OA, and whether these cells behave differently in early and late OA of different types.
  
  If a treatment is developed, the knowledge gained from these critical experiments may help us personalize how, when, and in which types of patients a macrophage targeting treatment might work best.
  
  To prepare us to test how we could strategically leverage the anti-inflammatory functions of macrophages in future studies to improve OA outcomes.

Project Lay Summary:

Osteoarthritis (OA) is by far the most common type of arthritis. Many people think OA is just “wear and tear” arthritis and don’t know that OA also involves inflammation. Importantly, OA is different from other types of arthritis with high-grade inflammation (e.g. rheumatoid arthritis). OA presents with low-grade, chronic, and often intermittent inflammation. Research has shown that inflammation in the lining of joints from people and animals with OA contains high numbers of immune cells called macrophages.

In this study, we will test whether macrophages play a critical role in the development and progression of two types of OA seen very commonly in people: OA after joint injury (post-traumatic OA), and OA with changes in the body’s metabolism such as obesity (metabolic OA). Interestingly, some macrophages promote inflammation while others help to control inflammation and promote tissue healing. However, a critical knowledge gap exists. It is unknown whether the main roles of macrophages are affected by different stages or different types of OA.

This project proposes to answer these questions: 1. Are OA macrophages mainly pro-inflammatory or anti-inflammatory, and are they different in early vs. late stages, and in post-traumatic OA vs. metabolic OA? 2. What are the gene expression profiles of OA macrophages in different stages and types of OA? 3. Does treatment that specifically causes loss of macrophages reduce or accelerate OA, and does the effect depend on treatment timing or type of OA?

Before we can safely answer these questions in humans, we need to acquire more information about the role of macrophages in OA by using two well-established animal models of post-traumatic OA and metabolic OA in rats. First, we will examine the knee joint tissues to assess whether the macrophages present in early and late knee OA are mostly pro-inflammatory vs. anti-inflammatory. We will also see whether the macrophages occurring in each type of OA are different.

Next, we will use advanced genetic tools to measure the expression of all macrophage genes, which will give us critical insight into how these cells are functioning at different stages of each type of OA. Finally, we will use a treatment to selectively remove all macrophages from the rats while OA develops, or after OA has been established. Comparing the severity of OA with and without macrophages, at different stages of the disease, and in different types of OA, will give us critical knowledge about these inflammatory cells. Our long-term goal is to find treatments for the symptoms and damage caused by OA in our patients.

This project will help us understand if macrophages worsen or protect against knee OA, and whether these cells behave differently in early and late OA of different types. If a treatment is developed, the knowledge gained from these critical experiments may help us personalize how, when, and in which types of patients a macrophage targeting treatment might work best. The study will also prepare us well to test how we could strategically leverage the anti-inflammatory functions of macrophages in future studies to improve OA outcomes.

Associate Professor, Dept. of Dentistry, Schulich Medicine & Dentistry, Western University

Project Title: YAP1: a novel target for scleroderma fibrosis?

Annual Commitment:
Year 1: $117,252
Year 2: $117,252
​Year 3: $117,252

Keywords: Scleoderma, conditional, fibrosis, adhesive signaling, connective tissue, skin, cell culture, fibroblast, TGF beta, microenvironment

Project summary:

• Why?: The most characteristic feature of scleroderma is the build-up of tough scar-like fibrous tissue in the skin. A cell type called the myofibroblast (a special form of fibroblast) is responsible for the overproduction of collagen and the development of tough scar tissue (a process called called fibrosis).  The toughness of the scar tissue itself in turn acts on myofibroblasts to generate more collagen and scar tissue.  We want to break this vicious cycle to treat scleroderma.
• What?: The aim of our project is to identify if a protein called YAP1 (found inside the fibroblast) is responsible for generating the toughness of scar tissue.
• How?: To test if:
  1. Visudyne can block the generation and activity of myofibroblasts, and
  2. The presence of YAP1 in fibroblasts is essential for the development of skin fibrosis in our animal models of scleroderma.
• Impact?: Our project could ultimately result in the use of these drugs to treat scleroderma.

Project lay summary:

Need/Gap addressed: According to The Arthritis Society's website: "the name scleroderma is derived from the Greek word skleros, which means hard, and derma, which means skin. The most characteristic feature of scleroderma is the build-up of tough scar-like fibrous tissue in the skin. The disease may affect the skin alone...or be a systemic disease that involves internal organs...Scleroderma begins with being born with the genetic potential to develop the disease. Something then triggers the immune system....to generate antibodies that attack healthy tissue.... This response produces inflammation and an overproduction of collagen " the tough fibrous protein that helps construct connective tissues, such as tendons, bones, and ligaments (and) scar tissue. This excess collagen is deposited in the skin and body organs." A cell type called the myofibroblast (a special form of fibroblast) is responsible for the overproduction of collagen and the development of tough scar tissue (a process called called fibrosis). The toughness of the scar tissue itself in turn acts on myofibroblasts to generate more collagen and scar tissue. We want to break this vicious cycle to treat scleroderma.

Research Question and Approach: The aim of our project is to identify if a protein called YAP1 (found inside the fibroblast) is responsible for generating the toughness of scar tissue. YAP1 is activated due to the acquisition of tough connective tissue and has increases levels of a gene called CCN2 that is essential for the development of scar tissue. Since drugs targeting YAP1 (e.g. Visudyne) have been in clinical use since the year 2000, they are safe to use in humans. Our project could ultimately result in the use of these drugs to treat scleroderma. In this project, we will test if:1) Visudyne can block the generation and activity of myofibroblasts, and 2) the presence of YAP1 in fibroblasts is essential for the development of skin fibrosis in our animal models of scleroderma.

Impact: We will: 1) Show if YAP1 inhibitors block the activity of myofibroblasts 2) Show if YAP1 is required for skin fibrosis 3) Provide evidence whether, in principle, YAP inhibitors could be used to treat scleroderma.

Professor, Departments of Pharmacology & Anaesthesia, Faculty of Medicine, Dalhousie University

Project Title: Sex Differences in Joint Neuropathic Pain Involve NaV1.8 Ion Channels

Annual Commitment:
Year 1: $112,200
Year 2: $119,700
​Year 3: $119,200

Keywords: neuropathic pain, osteoarthritis, electrophysiology, pain behaviour, animal models, sodium channels, joint nerves, drug discovery, gender, immunohistochemistry

Project Summary:

• Why?: Emerging evidence shows that nerves in OA joints are damaged leading to the development of neuropathic pain, while drugs like Advil© (ibuprofen) are being used which treat inflammatory pain. Therefore, a new family of drugs which manage neuropathic pain are required. A promising target for the alleviation of neuropathic pain is a sodium channel present exclusively on pain-sensing nerves. These sodium channels are responsible for the electrical activity and resultant firing of pain-sensing nerves only.
• What?: A neuronal channel called NaV1.8 has been implicated in neuropathic pain and we have previously found that blocking this channel can alleviate OA pain. Joint neuropathic pain is mediated in part by NaV1.8 channels in a sex-specific manner.
• How?: Joint nerve damage and neuropathic pain will be compared between male and female animals with knee OA. Animals will then be treated with a NaV1.8 inhibitor to see if there is a sex-specific difference in pain relief when blocking this nerve channel. Finally, we will develop a NaV1.8 antibody system which will be more effective at blocking this sodium channel and thereby prolong the analgesic window. 
• Impact?: To identify a novel treatment strategy for the alleviation of OA pain for patients who are unresponsive to the currently prescribed anti-inflammatory drugs. While this treatment would be suitable for both sexes, we predict that females will benefit more from this approach than males.

Project Lay Summary:

The number one concern of osteoarthritis (OA) patients is effective pain relief; however, this primary consumer need is often unmet. One of the reasons for this lack of effective OA pain control is that currently prescribed analgesics are treating the wrong type of pain. Emerging evidence shows that nerves in OA joints are damaged leading to the development of neuropathic pain, while drugs like Advil© (ibuprofen) are being used which treat inflammatory pain. Therefore, a new family of drugs which manage neuropathic pain are required.

A promising target for the alleviation of neuropathic pain is a sodium channel present exclusively on pain-sensing nerves. These sodium channels are responsible for the electrical activity and resultant firing of pain-sensing nerves only. Thus, targeting these neuronal channels will reduce the nerve activity associated with neuropathic pain while maintaining normal sensitivity to touch and temperature.

One such channel, called NaV1.8, has been implicated in neuropathic pain and we have previously found that blocking this channel can alleviate OA pain. A limitation of the blocker, however, is that its pain-relieving effects are short lasting. Women are more likely to suffer from OA and experience more musculoskeletal pain compared to men. The reasons for this sex distinction are unknown, but differences in neurobiology is likely to play a major part. Neuropathic pain is more common in females and this is because females are more susceptible to peripheral nerve damage.

We believe this sex difference in neuropathic pain sensitivity is linked to variations in NaV1.8 levels. Thus, we hypothesize that: Joint neuropathic pain is mediated in part by NaV1.8 channels in a sex-specific manner. Joint nerve damage and neuropathic pain will be compared between male and female animals with knee OA. Animals will then be treated with a NaV1.8 inhibitor to see if there is a sex-specific difference in pain relief when blocking this nerve channel.

Finally, we will develop a NaV1.8 antibody system which will be more effective at blocking this sodium channel and thereby prolong the analgesic window. Our proposed studies will identify a novel treatment strategy for the alleviation of OA pain for patients who are unresponsive to the currently prescribed anti-inflammatory drugs. While this treatment would be suitable for both sexes, we predict that females will benefit more from this approach than males.

Professor, Department of Pediatrics, Faculty of Medicine, University of Saskatchewan

Project title: The Biologic Basis of Co-existent Uveitis and Arthritis in Children: Towards Early Detection, Targeted Treatment, and Prevention

Annual Commitment:
Year 1: $118,374
Year 2: $119,963
​Year 3: $119,784

Keywords: antinuclear, arthritis, autoimmunity, childhood arthritis, collagen, inflammation, JIA, matrix metalloproteinase, streptocouccus, uveitis

Project Summary:

• Why?: An estimated 24,000 Canadian children live with arthritis.  One in eight children with JIA (an estimated 3,000 Canadian children) also will have uveitis, which is inflammation of the middle layer of the eyes.  The reasons why joint inflammation (arthritis) and eye inflammation (uveitis) occur together in some children are poorly understood. 
• What?: To help explain why joint and eye inflammation occur together in children.
• How?: To investigate how collagen structure is changed by certain inflammation proteins, by studying a larger group of children with arthritis and over time see if testing their blood for the same markers can be used to predict who will develop uveitis. 
• Impact?: Early recognition of uveitis in children with arthritis and prompt treatment are essential to prevent blindness. By determining the mechanisms that explain the link between arthritis and uveitis in children, we can then design more specific treatments and gain insight into possible causes of the condition.

Project Lay Summary:

An estimated 24,000 Canadian children live with arthritis.  One in eight children with JIA (an estimated 3,000 Canadian children) also will have uveitis, which is inflammation of the middle layer of the eyes. Despite intensive and often distressing therapies (for example, administration of eye drops to young children many times a day), up to one-third of affected children develop profound, permanent vision loss.  As a young adult who has endured childhood onset arthritis and uveitis stated: “Arthritis and uveitis are independently life altering; together they can have devastating consequences.  Lack of mobility or loss of sight can quickly strip the innocence of childhood.”

Uveitis is usually invisible to the patient until it causes eye damage. It can lead to permanent vision loss in one third of affected children. Early recognition of uveitis in children with arthritis and prompt treatment are essential to prevent blindness.

The reasons why joint inflammation (arthritis) and eye inflammation (uveitis) occur together in some children are poorly understood. We expect this research will help explain why  joint and eye inflammation occur together in children.  In our earlier studies of animals with joint and eye inflammation we identified collagen (a protein that is present in both the joint and the eye) as a  possible common target that is attacked by the immune system of affected children.

In this research project, we will investigate how collagen structure is changed by certain inflammation proteins. Once altered, the collagen causes an immune reaction that leads to damage in the joint and the eye.   In our prior studies in animals and in children affected with arthritis and uveitis we identified markers in the blood that are present when these two conditions occur together. Using this information we are now prepared to study a larger group of children with arthritis and over time see if testing their blood for the same markers can be used to predict who will develop uveitis.

By determining the mechanisms that explain the link between arthritis and uveitis in children, we can then design more specific treatments and gain insight into possible causes of the condition. For example, it is possible that certain infections could trigger the start of the inflammation in the joint and eye in children who have certain genetic characteristics.

This study will be conducted in childhood arthritis clinics across Canada.  We will collaborate with Canadian ophthalmologists and other researchers from the United States and the Netherlands to ensure this study is undertaken quickly and efficiently to generate results that can be promptly applied to benefit affected children. 

Assistant Professor, Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto

Project title: Personalization of osteoarthritis care using large-scale randomized evidence: network meta-analysis and methodological development

Annual Commitment:
Year 1: $100,000
Year 2: $99,926
​Year 3: $48,250

Keywords: osteoarthritis, treatment, pain, meta-analysis, randomized, evidence-based, quality of life, systematic review, knee, hip

Project summary:

• Why?: There are many treatments for osteoarthritis available, but the most effective and safest treatments are not known yet.
• What?: Our objective is to determine what treatments work best for patients with osteoarthritis.
• How?: 
  1. We will collect and critically evaluate all pertinent published trials over the last 30 years. We will employ sophisticated statistical techniques that are capable of estimating the benefits and harms of each treatment compared against each other, even if few or no head-to-head comparisons have been conducted.
  2. We will develop a statistical model that will allow us to investigate the association between treatment effects of each conservative OA treatment and personal characteristics of people living with OA. This analysis will allow us to tailor the treatment of people living with OA according to their personal characteristics.
  3. We will implement a freely available online platform to provide patients and clinicians access to the results of our analyses to facilitate shared clinical decision-making. This platform will use the characteristics of people with osteoarthritis (e.g. age, gender, disease severity) to inform users about the probability that each osteoarthritis treatment will cause more benefit than harm.
• Impact?: The present project will develop and use novel methods to produce continuously updated knowledge to optimize the treatment of millions of persons living with osteoarthritis in Canada and worldwide.

Project lay summary:

There are many treatments for osteoarthritis available, but the most effective and safest treatments are not known yet.  In this project, our objective is to determine what treatments work best for patients with osteoarthritis.

To accomplish this goal, we will collect and critically evaluate all pertinent published trials over the last 30 years. We will employ sophisticated statistical techniques that are capable of estimating the benefits and harms of each treatment compared against each other, even if few or no head-to-head comparisons have been conducted.

Furthermore, we will develop novel statistical models that enable the assessment of whether patient characteristics such as age, gender, disease severity, among others, are associated with a better response to different osteoarthritis interventions. Finally, we will implement a freely available online platform to provide patients and clinicians access to the results of our analyses to facilitate shared clinical decision-making.

This platform will use the characteristics of people with osteoarthritis (e.g. age, gender, disease severity) to inform users about the probability that each osteoarthritis treatment will cause more benefit than harm. As a whole, the present project will develop and use novel methods to produce continuously updated knowledge to optimize the treatment of millions of persons living with osteoarthritis in Canada and worldwide.

Associate Scientist, Institute for Work & Health

Project title: Work disability prevention for Millennial young adults with rheumatic disease

Annual Commitment:
Year 1: $30,772
Year 2: $49,744
​Year 3: $62,131

Keywords: employment, work disability, rheumatic disease, young adulthood, job accommodations, workplace supports, longitudinal research, productivity loss, millennial, school-to-work

Project summary:

• Why?: Despite advances in clinical care, people living with rheumatic disease (RD) continue to report trouble finding employment and staying productive at work. Because previous research focuses primarily on older adults with RD, it is unclear if Millennial young adults with RD, who are just beginning their careers, have the same needs when it comes to workplace support.
• What?: To examine the needs of Millennials with RD within the workplace.
• How?: Survey Millennial young adults with RD to learn more about their workplace support needs.
• Impact?: Results will help employers, clinicians, and policy makers develop strategies that will assist Millennials with RD transition into the world of work, and ensure that they remain employed and productive once there.

Project lay summary:

Despite advances in clinical care, people living with rheumatic disease (RD) continue to report trouble finding employment and staying productive at work. Some previous research suggests that workplace policies and practices play an important role in overcoming these challenges. The research indicates that job accommodations (e.g., modified hours), work modifications (e.g., rearranging tasks) and extended health benefits (e.g., access to drug benefits) are examples of effective strategies for helping people with RD sustain employment and remain productive.

Because previous research focuses primarily on older adults with RD, it is unclear if Millennial young adults with RD, who are just beginning their careers, have the same needs when it comes to workplace support. Our study is one of the first to examine the needs of Millennials with RD within the workplace. Millennials (born 1982-1999) make up a growing portion of the labour force but are less likely to hold permanent full-time jobs. A RD adds to the challenges faced by Millennials as they transition into employment.

We will survey Millennial young adults with RD to learn more about their workplace support needs. Our survey will also identify how characteristics of a person’s health and their working conditions impact workplace support needs, and early work experiences. Our results will help employers, clinicians, and policy makers develop strategies that will assist Millennials with RD transition into the world of work, and ensure that they remain employed and productive once there.

Scientist, Sunnybrook Research Institute, Evaluative Clinical Sciences Platform, Holland Musculoskeletal Research Program

Project title: Enhancing the Use of Rheumatology Electronic Medical Records to Evaluate and Optimize Care and Management of Arthritis

Annual Commitment:
Year 1: $99,098
Year 2: $99,910
​Year 3: $99,100

Keywords: electronic medical records, quality measure, quality indicator, quality of care, inflammatory, validation, rheumatoid arthritis, psoriatic arthritis, wait times, health services

Project summary:

• Why?: The quality of care provided to Canadians with inflammatory arthritis (IA) is not routinely monitored in Canada, nor are patient clinical outcomes.  Electronic medical records (EMRs) used by doctors capture information relevant for the day-to-day care of their patients including medical histories and the type of healthcare patients receive.
• What?:
  • Our primary research questions include:
    1. How complete are rheumatology EMRs?
    2. Can we accurately and efficiently identify patients with IA conditions from the complete practice data
    3. Is the data of sufficient quality to derive quality measures and support the measurement of quality of care and quality improvement efforts? Answering these questions will determine the feasibility and usefulness of using rheumatology EMRs for research and quality improvement purposes.
  • Secondly, we will also demonstrate the capabilities of using rheumatology EMRs to evaluate care and outcomes of IA patients. Some of the research questions that we will answer include:
    1. How long are patients waiting to see rheumatologists?
    2. Are there variations in wait times between rheumatologists?
    3. Which factors are associated with timely care?
• How?: We will securely collect EMR data from rheumatologists into a central database. We will assess the quality of this data to understand how we can use the data to measure detailed aspects of care. This will allow us to analyze the data to better inform healthcare delivery to ensure it is safe, effective and efficient and that patients achieve the best possible outcomes.
• Impact?: This project plays an essential first step to enable the measurement of quality of care to catalyze quality improvement efforts using real-world data for all patients under rheumatology care. Our results will inform continuous quality improvement including timely access to rheumatology care and treatment as well as patient outcome to ensure Canadians with IA are receiving the best possible care and achieving the best outcomes.

Project lay summary:

The quality of care provided to Canadians with inflammatory arthritis (IA) is not routinely monitored in Canada, nor are patient clinical outcomes.  Electronic medical records (EMRs) used by doctors capture information relevant for the day-to-day care of their patients including medical histories and the type of healthcare patients receive. This data can be anonymized and coded to protect patient privacy and confidentiality, and securely used for research and quality improvement activities.

We will securely collect EMR data from rheumatologists into a central database. We will assess the quality of this data to understand how we can use the data to measure detailed aspects of care. This will allow us to analyze the data to better inform healthcare delivery to ensure it is safe, effective and efficient and that patients achieve the best possible outcomes. We will do this by developing methods to evaluate quality of care using the EMR data.  We will feedback this information to rheumatologists to help drive quality improvements. We will also evaluate wait times between rheumatologists and the effect of different models of care on  wait times.

This project plays an essential first step to enable the measurement of quality of care to catalyze quality improvement efforts using real-world data for all patients under rheumatology care. Our results will inform continuous quality improvement including timely access to rheumatology care and treatment as well as patient outcome to ensure Canadians with IA are receiving the best possible care and achieving the best outcomes.

Centre de recherche, Centre hospitalier d'université de Montréal

Supervisor: Dr. Walid Mourad, Centre de recherche, Centre hospitalier d'université de Montréal

Project title: Involvement of CD154 in the atherosclerotic risk factor associated with rheumatoid arthritis

Annual Commitment:
Year 1: $20000
Year 2: $20000
Year 3: $20000

Keywords: Rheumatoid Arthritis, CD154, atherosclerosis, association, new receptors, integrins, CD154 mutants, animal model of arthritis, atherogenic mice, plasma of arthritis patients

Project Lay Summary:

Patients with Rheumatoid Arthritis show increased susceptibility to develop cardiovascular complications, as compared to the general population. Unfortunately, current drug therapies do not completely limit or prevent the development of these complications. Multiple lines of evidence now support the importance of inflammatory pathways in the pathophysiology of both complications. Our research program aims to study and understand the mechanisms by which autoimmune disease such as Rheumatoid Arthritis and heart diseases develop, and more importantly, to establish the key inflammatory contributors that link both disorders. More precisely, we intend to delineate the importance of a critical inflammatory mediator in the onset of cardiovascular complications in patients with autoimmune diseases using specific animal models, human samples and blocking agents generated in our laboratory. This project may lead to the development of novel and safe therapeutic targets for the treatment of Rheumatoid Arthritis and its cardiovascular-associated complications.

Rehabilitation Sciences Institute, University of Toronto / University Health Network

Supervisor: Dr. Zahi Touma, University Health Network

Project title: Improving the assessment and care management of everyday living limitations in adults with Systemic Lupus Erythematosus related cognitive impairments: an multi-methods examination of activities of daily living

Annual Commitment:
Year 1: $20000
Year 2: $20000

Keywords: Activities of daily living, participation, Lupus, Systemic Lupus Erythematosus, cognition dysfunction, cognitive impairment, rehabilitation, systematic review, qualitative (interview), quantitative (survey)

Project Lay Summary:

Need/gap: Over 35,000 Canadians live with the widespread effects on bodily functions and activities of daily living (ADL) associated with systemic lupus erythematosus (SLE). One significant body function area that can be affected is thinking skills, also known as cognitive functions.  Cognitive impairments (CI or issues in thinking skills) can include declines in a person’s memory, planning, and attention abilities, as well as their thinking speed.  It is estimated that up to two-thirds of people living with SLE experience CI, and these changes can have a significant effect on a person’s ADL performance.  Decreased ADL performance can decrease life satisfaction and quality of life. Currently there is no study that has examined the ADL function of people living with SLE related CI.
Research question: For people living with SLE, do people who experience associated CI have different ADL limitations than people who do not experience associated CI?

Approach to address gap: This project will use three studies to answer the research question.  The first study will review all of the available published studies that have examined ADL functioning in people with SLE. This literature includes both people with and without related CI, and reviewing it will help identify the possible ADL limitations related to SLE.  The second study will interview people with SLE and related CI regarding how changes in thinking skills has affected their daily lives and ADL functioning.  This study identifies what ADL issues might be specific to SLE related CI.  The third study will compare the self-reported ADL limitations of (1) people with SLE and CI versus (2) people with SLE and no CI.  This study will develop a survey of ADL limitations using information from the first two studies. The survey will be given to people with SLE identified as having or not having CI, and difference between the two groups’ self-reported answers will be compared.

Impact to arthritis care: The results of this study are needed to build future assessment instruments that will identify and monitor over time the ADL functioning in people with SLE and CI.  Once the areas of ADL functioning have been identified than better treatments for improving ADL function can be developed, tested, and implemented in SLE clinical practices.  This will help people stay involved in meaningful life activities, participate in their chosen life roles, and optimize quality of life.

Target audience: This information will be important for people living with SLE, caregivers, and SLE clinicians as changes in ADL functions can often be the first sign of CI. Knowing what ADLs are specifically impacted by SLE related CI can help monitor functioning over time.  Further, the results can help clinical practitioners in identifying and addressing ADL limitation areas important to people living with SLE related CI.  Further, for clinical practitioners and academic researchers, the results will provide foundational evidence and identify areas for further research in an area of that currently lacks information.

Dept. of Comparative Biology & Experimental Medicine, Faculty of Veterniary Medicine, University of Calgary

Supervisor: Dr. John Matyas, University of Calgary

Project title: Unravelling the mechanisms underlying chronic OA joint pain: A neuroimmunological focus

Annual Commitment:
Year 1: $20000
Year 2: $20000
​Year 3: $20000

Keywords: Single cell RNAseq, trauma-induced Osteoarthritis, neuroimmunology, transgenic mouse models, bioinformatics, neuropathic pain behaviour, flow and immunohistochemistry, macrophages, neuronal-macrophage co-cultures, retrograde tracing

Project Lay Summary:

Chronic joint pain, such as that experienced by those who suffer from arthritis, is a common cause of disability that is difficult to treat and is poorly understood. The symptoms of chronic pain reported by arthritis patients closely resemble those reported by patients with nerve injuries. This suggests that arthritis pain might be caused, at least in part, by injury and inflammation of the nerves in addition to damage and inflammation at the joint site. We already know that inflammation within the upstream circuitry (ie. spinal cord) of pain sensation can activate pain pathways to a point where pain originating from the joint is amplified in the spinal cord further enhancing the feeling of a painful stimulus. What we don’t know is how much this type of nervous system ‘pain’ actually contributes to a patients experience of pain. As such, we aim to further understand the mechanisms of how this type of nervous system inflammation sustains or contributes to pain sensation. The first aim of these studies is to define and quantify the molecules associated with immune cells and nerve cells that are activated during chronic joint pain. To do this we will use the latest technology to isolate thousands of individual cells, such as immune cells and nerve cells, from the pain pathway at key time points in a rodent model of chronic joint pain (ACL transection injury at 16 weeks post-injury). We will then perform an unbiased sequencing experiment where we can detect the activation profile of these cells in pain states versus the same cells in healthy conditions. We will also compare this to another pain model that is already well characterized to be driven primarily by nervous system mechanisms of pain. We believe that any common mechanisms will likely be strong therapeutic targets. Such an approach is creative because it will allow us to focus on meaningful mechanisms of pain rather than tissue specific changes that may correlate with pain but not necessarily play a role in driving pain. The second aim is to modulate these pathways with the goal of preventing or limiting the development of chronic arthritis pain. We hope to not only uncover the underlying mechanisms of chronic joint pain but also identify therapeutically relevant pathways that can be targeted to treat chronic pain in the clinic.

Dept of Psychology and Neuroscience, Faculty of Science, Dalhousie University

Supervisor: Dr. Christine Chambers, Dalhousie University 

Project title: Parental perceptions of pain and treatment adherence in juvenile idiopathic arthritis (JIA)

Annual Commitment:
Year 1: $10,500
Year 2: $10,500
​Year 3: $10,500

Keywords:Juvenile Idiopathic Arthritis, pain, treatment adherence, physical activity, medication, parent, coping, catastrophizing, attitudes, pain management

Project Lay Summary:

“Zachary lived with the pain of arthritis for nine months. Despite the fact that he knows that the medicine in the injections is making him feel better, it doesn’t make it any easier to receive the painful poke each day” [35].  Around 24,000 children across Canada live with Juvenile Idiopathic Arthritis (JIA) [1], making it one of the most common childhood chronic illnesses [2]. Pain is the most frequently reported symptom [3], caused by both the illness itself and its associated treatments. Treatment aims to manage the pain and prevent damage to the joint tissues through both medication and physical therapy [4], which when followed leads to improved outcomes [5-11]. Unfortunately, following these recommendations can be hard [6, 12-23]; many of the treatments are painful (e.g., weekly injections), or have uncomfortable side effects (e.g., nausea) [24-29]. While pain is usually something we try to avoid [61], this is not ideal when it comes to treatment-related pain. It can be difficult for a child to understand how something that hurts can be good for them, so we must rely on parents to encourage treatment adherence. Parents however, are stuck between knowing what’s best for their child, and not wanting to see their child in pain. Previous research tells us that parents behaviours and beliefs regarding their child’s experience of pain may be related to avoidance behaviours [30-32]. Now we would like to see how parents might have an effect on treatment adherence in children with JIA.

This study will look at whether parent-level factors relate to treatment adherence in children with JIA. We expect that parents who cope by avoiding things, have negative feelings about pain and medication, have little knowledge of pain-management, and score higher on fear of pain and pain catastrophizing scales will have children who are less adherent to their treatment plan.

Parents of children with JIA will be recruited via social media with the help of Cassie & Friends [33]. All families in Canada with a child under the age of 18 who has been diagnosed with JIA will be eligible. After agreeing to participate, parents will fill out online questionnaires about their child’s diagnosis and treatment, adherence, coping, self-efficacy, fear of pain, catastrophizing, and their own knowledge and attitudes regarding pain. Some of the participants will also be interviewed to better understand the barriers they face when following treatments. Analyses will determine how these parent-level factors relate to treatment adherence.

The proposed study may identify how the parent’s beliefs and knowledge around pain relate to treatment adherence, which can have significant effects on their child’s health and well-being [5-7, 34]. Once parent factors are identified, we would like to teach families ways to manage pain to see if this will reduce parental fears and anxieties. JIA is a chronic disease that has long-term effects on physical health, education, employment, mood, and relationships [71-73]. We hope that results from this study will contribute to improving treatment adherence and these long-term outcomes for children with JIA across Canada.

Dept of Pharmacology, Faculty of Medicine, Dalhousie University

Supervisor: Dr. Jason McDougall, Dalhousie University 

Project title: The Role of Proteinases in the Progression of Osteoarthritis and its associated Neuropathy

Annual Commitment:
Year 1: $10,500
Year 2: $10,500
​Year 3: $10,500

Keywords: Osteoarthritis, pain, sex-differences, neuropathic pain, serine protesases, electrophysiology, joint injury, meniscal tear, inflammation, histology

Project Lay Summary:

Osteoarthritis (OA) is the most common form of arthritis, typically affecting women at higher rates than men. OA is a painful and debilitating condition that results from the body’s failed attempt to repair damaged joint tissues. The most traditionally prescribed treatments for OA patients, non-steroidal anti-inflammatory drugs (NSAIDs), do not work for all patients and with long-term use these drugs often become less effective and can cause unwanted side effects.

Approximately 60% of people suffering from OA cite poor management of their chronic pain and this is the number one reason for patients to visit their physician. Unsatisfactory pain management is possibly due to a third of OA patients developing neuropathic pain, where the nerves within the affected joint are damaged as the disease progresses. Neuropathic pain symptoms (e.g. shooting or burning pain, “pins and needles”, numbness) are more common among women and this type of pain is resistant to traditionally used treatments. Therefore, the discovery of new drugs for treating joint neuropathic pain symptoms is necessary in combatting OA pain.

We believe that the nerves are damaged, in part, by enzymes such as serine proteinases—which are commonly found in arthritic joints. In this project, I aim to identify specific serine proteinases which may be useful targets for OA pain and then explore the analgesic ability of these serine proteinase modulators in a model of OA. The level of serine proteinases in arthritic patient’s joints will be assessed to determine if the concentration and type of proteinases present correlate with the stage of disease. Using an injury model of OA, I will study the progression of knee joint pain and nerve damage in both male and female animals, and determine if drugs targeting serine proteinases can provide pain relief once nerve damage has occurred. I will also explore whether chronic treatment with these drugs can prevent nerve damage.

This project will (1) enhance our understanding of OA pain and (2) also identify important sex-specific mechanisms underlying the difference in prevalence of OA and neuropathic pain in women and men. The results of these experiments may point towards new and sex-specific targets for drugs used to treat joint neuropathic pain.

Dept. of Physiology and Pharmacology, Schulic School of Medicine & Dentistry, Western University

Supervisor: Dr. Cheryle Séguin, Western University 

Project title: Investigating potential regulators of ectopic mineralization in a mouse model of diffuse idiopathic skeletal hyperostosis (DISH)

Annual Commitment:
Year 1: $10,500
Year 2: $10,500
​Year 3: $10,500

Keywords: Diffuse idiopathic skeletal hyperostosis, intervertebral disc, genetics, ectopic mineralization, transcriptomics, metabolomics, proteomics, systems biology, connective tissue disorders, MALDI-IMS

Project Lay Summary:

The Arthritis Society lists diffuse idiopathic skeletal hyperostosis (DISH) as the second most common form of arthritis (after osteoarthritis) with a prevalence of 15-25% of North Americans over the age of 50. However, health professionals are often unfamiliar with DISH, and consequently it is underdiagnosed and often misdiagnosed. DISH is typically diagnosed through x-ray detection of aberrant calcification of the soft connective tissues of the spine, including ligaments and intervertebral discs (IVDs). Symptoms are typically mild in the early stages of disease, including thoracic spine pain and stiffness. As such, patients are not often seen until advanced stages where the formation of ectopic calcified material affects adjacent anatomy causing dysphagia (difficulty swallowing) and/or compression of the spinal cord and adjacent nerve roots. To date, no studies have evaluated the effectiveness of any therapy in this disease, likely reflecting our poor understanding of its pathogenesis. This knowledge gap is due to limited access to human disease tissues and a lack of animal models that allow researchers to study events associated with disease onset. Consequently, apart from surgical removal of calcified tissues in severe cases, no disease-modifying treatments exist. Therefore, there is an urgent need for research studies aimed at understanding the biological mechanisms that contribute to the pathogenesis of DISH.

Our study applies technologies allowing for an unbiased screen of tissues affected by ectopic calcification to uncover the cellular and molecular underpinnings of DISH. This work is based on the use of a mouse model that our group recently reported as the first pre-clinical model of DISH (mice genetically altered to lack the gene encoding the ENT1 transport protein). This mouse model shows a remarkably reproducible temporal and spatial pattern of spine calcification resembling DISH and thus allows us to not only evaluate changes associated with the diseased state but also investigate predictors of DISH susceptibility and evaluate therapeutics. Since DISH affects the intervertebral disc, and we are experts in disc biology, we will investigate changes in this tissue to extrapolate findings to other connective tissues affected with the disease.

Our experimental strategy involves cutting edge technologies to conduct global analyses of tissues both prior to and associated with the onset of DISH-like calcification. Taking a multi-pronged approach, we aim to identify changes in: i) gene expression, ii) protein expression, and iii) metabolites associated with ectopic calcifications of spinal tissues in our mouse model of DISH. We will integrate the findings from each analysis and validate our findings in human tissues to develop a holistic view of the biology associated with DISH.

Overall, these studies aim to impact our understanding of arthritis by: i) identifying the biological pathways that lead to DISH, ii) identifying biomarkers to allow early-stage detection of DISH, ii) identify therapeutic targets to prevent or delay the onset of ectopic calcifications in DISH and associated disorders. This research integrates a collaborative, transdisciplinary team that includes biologists, technical specialists, clinicians and patient partners to ensure that in the long term, our findings impact the care of arthritis patients.

Arthritis Centres are the rheumatology division of the department of medicine in Canadian universities, including accredited pediatric rheumatology centres.

For over 30 years, the Arthritis Society has provided annual funding to Arthritis Centres across Canada. As centres of clinical expertise, research and education, their role in the Canadian health care environment is to help ensure that more Canadians with arthritis receive better care.

Current funding recipients (2017/18) of $15,000 for a term of one year are:

• McMaster University
• SickKids Hospital, University of Toronto
• Research Institute of MUHC, McGill University
• Montreal Children’s Hospital, McGill University
• University of Manitoba
• University of Calgary
• Dalhousie University
• CHU de Quebec, Université Laval
• University of Saskatchewan
• University of Alberta

Arthritis Centre grants support Centres that align with one or more of the following goals:

• Increasing the number of Rheumatologists
• Improving Models of Care
• Supporting Arthritis Research

Every year, the field of rheumatology changes with new knowledge collected by research scientists from across Canada and around the world. Translation of this knowledge is important for the development of evidence-based rheumatology practice. Since allied health professionals play a large role in rheumatology, it is important that they be able to provide evidence for their roles in the field and demonstrate the positive impact that they have on the care of people with inflammatory arthritic disease. The AHPA encourages its members to contribute knowledge to the field by holding an annual research grant competition and recognizing their research efforts at the Canadian Rheumatology Association’s and AHPA’s Annual Scientific Meeting. An award of $5000 will be honored for the best research proposal submitted by an AHPA member. A list of recipients of this award can be found here.