Forging a path toward a brighter future in osteoarthritis

By Ramtin Hakimjavadi, BMSc Candidate

From early in his childhood, Dr. Tom Appleton, PhD, had a deep appreciation for the natural world. Born and raised in Ailsa Craig, he spent most of his childhood outdoors, playing sports and enjoying nature.

As a first-year undergraduate student, Dr. Appleton recalls developing a keen interest in biology and even yearned to be a marine biologist for a time. Although his chosen profession does not involve collecting aquatic samples, a distinct passion for scientific exploration and discovery is apparent in his career as a researcher and rheumatologist.

After completing his undergraduate education at Western University, medical school was Dr. Appleton’s original goal. Positive experiences researching cartilage biology in the laboratory of Frank Beier, PhD – an early mentor who he continues to collaborate with today – later persuaded him to pursue the MD/PhD Program at Schulich Medicine & Dentistry.

Mentorship and strong ties to the research community have been invaluable components of Dr. Appleton’s career development. Upon starting his PhD, the task of familiarizing himself to osteoarthritis (OA) research was initially intimidating. Nevertheless, he took a dive into the field, eager to learn as much as he could from those around him. “I was always confident that I had the right support network around me,” he explained. “I developed a network of really thoughtful, intelligent people.”

Dr. Appleton went on to receive his PhD in Physiology working on OA in the Beier Lab. This line of research ran parallel to the completion of his medical degree, residency in internal medicine and his fellowship in rheumatology. Emersed in high-quality training throughout his educational journey, Dr. Appleton’s home has long been at Western University. However, his career’s work touches the lives of people worldwide.

OA is the most common form of arthritis in the Western world. It is a progressive disease that attacks the joint cartilage and the underlying (subchondral) bone. Patients with OA suffer from decreased mobility of the affected joint, stiffness and worsening pain.

Although there is no cure, research is progressing toward the development of disease-modifying therapies (DMTs). However, current therapeutic advancements, such as joint replacement, are still limited to late intervention – once most of the damage to the joint has occurred.

The Synovial Translational Biology Lab in Osteoarthritis – developed and led by Dr. Appleton – examines the mechanisms leading to the disease, particularly in its early phases, to uncover novel targets for treatment.

There are three fundamental pillars to his research program, encompassing all phases from discovery and development to implementation in a clinical setting. This is not a coincidence, but rather by intentional design. As a clinician-scientist and rheumatologist, Dr. Appleton has unique insight into the clinical problems associated with OA. This allows him to drive the progress of his research towards meaningful medical discoveries.

“I think that’s one of the most exciting things about medicine: the discovery and then translating that into something that can help improve outcomes for patients,” he said. “I really want to be in that space where we are making clinically relevant discoveries.”

The first pillar of his research program involves working with animal models and patients to uncover key mechanisms of the disease and discover novel targets for therapy. The Western Ontario Registry for Early Osteoarthritis (WOREO) study is a recently developed cohort that recruits patients with early-onset OA of the knee.

Ideally, the discovery of new targets would allow for the development of therapies which address OA before it progresses and deteriorates the joints of patients.

The second research pillar serves to define and understand different clinical phenotypes of OA – a disease that is characterized by its heterogeneous nature. “Osteoarthritis” is really an umbrella term to describe a group of conditions that are closely related but may be driven by different processes.

The emergence of therapies addressing the unique nature of each patient’s disease could pave the way for more personalized medicine. “The end goal would be to get the right treatment, to the right patient, at the right time,” Dr. Appleton explained.

The last pillar involves clinical trials. This phase serves to test therapies and examine the clinical significance of any promising findings from the preceding research pillars.

Dr. Appleton appreciates the importance of community and collective growth in the OA research field. “In osteoarthritis, we all have a healthy respect for how complicated this disease is and how many sets of expertise are needed to try to address it,” he said.

This fact is embodied by his research program’s multidisciplinary collaborative projects with members of the Bone and Joint Institute at Western. Experts with diverse skill sets contribute to help understand different aspects of OA including biomechanics, tissue outcomes, patient experience and health economics. “If we were to work in isolation, I don’t think we would be anywhere near as likely to succeed,” said Dr. Appleton. “So, there is a natural tendency and openness to work together.”

Outside the laboratory, Dr. Appleton continues to carry the value of community through his actions. In early June, he participated in the Walk for Arthritis’ 10th anniversary alongside his team, promoting awareness and helping raise funds for the Arthritis Society of Canada.

He is also involved with the Canadian Rheumatologists Association (CRA). As chair of the scientific committee, Dr. Appleton is responsible for planning the CRA Annual Scientific Meeting. At this event, experts from around the world gather together to present advancements in research, share ideas and foster collaboration. “It is an opportunity to bring the research field together with patient representatives, with allied health care, and with our basic and translational science community to try to push the field forward for rheumatology,” said Dr. Appleton.

As it stands today, treatments providing symptomatic relief are the primary options available for patients suffering from OA. Therefore, there is a great push for the development of therapies to improve patient outcomes earlier in the course of the disease.

This is precisely the kind of impact that Dr. Appleton strives for and what his research program is designed to achieve. “As a result of the work that we have done in this field, we want to finally have a treatment to improve patient outcomes. To stop the progression of osteoarthritis - that is the goal.”