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A Personalized Fight against Arthritis

by Melia D. Matthews

Arthritis, in horses and humans alike, is difficult to diagnose and treat. As a veterinarian, Erica Secor DVM ’13 saw hundreds of horses with arthritis, and she understands the obstacles that veterinarians and doctors face. Now a doctoral student in the lab of Heidi L. Reesink, Clinical Sciences, Secor is developing new tools to help veterinarians and doctors catch early-stage arthritis and provide targeted treatments.

Secor investigates equine post-traumatic osteoarthritis (PTOA), a type of arthritis that veterinarians encounter frequently, especially at veterinary hospitals such as Cornell’s Hospital for Animals. PTOA occurs after a joint injury: perhaps a horse stumbled or landed badly after a jump. The body’s immune cells try to fix the injury, leading to inflammation that may become more severe over time.

Like all types of arthritis, PTOA commonly involves pain and inflammation that can lead to discomfort, impaired mobility, and decreased quality of life for those affected. The disease is similar in animals and humans. In terms of arthritis, Secor says, “there is a lot we can learn from comparing and contrasting species.”

Improving on X-Rays

Picture a knee joint of any animal, and you can see two bones in close contact with each other with some cushioning cartilage tissue and a wrapping of tendons, muscles, and skin. But a very important piece of the joint is not a solid at all. A liquid called synovial fluid fills the space between the bones and lubricates the cartilage of the joint. Synovial fluid provides nutrients, removes waste, and helps to create smooth, slippery surfaces. It’s like WD-40 for knees, ankles, wrists, and shoulders.

Secor wants to develop tools that can assess the severity of a patient’s arthritis based on the synovial fluid and the membranous wrapping around the joint. “X-rays are the mainstays of diagnosing osteoarthritis,” she says. According to Secor, however, even experts can’t learn much from an x-ray until PTOA has become severe.

Secor is analyzing synovial fluid to find molecular markers of PTOA that could serve as a flag even before the disease has progressed to the point that x-rays become useful. Her goal is to identify arthritis before irreversible damage has been done, but also to develop a test that provides enough information about the patient’s condition that it will enable a veterinarian or doctor to choose the best treatment option.

In the lab, this means Secor is identifying proteins in synovial fluid and then assessing how the abundance of those proteins changes as arthritis progresses. If the amount of a protein in the synovial fluid changes significantly during early disease, it could serve as a good diagnostic marker.

She investigates the immune cells in synovial fluid with a similar goal in mind. First, she tags important immune cells, like macrophages and T cells, with color-coded markers. She then runs the sample through a flow cytometer, an instrument that can quickly count all the cells of a particular type based on their markers. It’s like looking into a crowd of 100,000 people and being able to determine the number of redheads in a few seconds. “We have seen big shifts in those [protein and cell] populations with the development of osteoarthritis,” Secor says.

“We have seen big shifts in those [protein and cell] populations with the development of osteoarthritis.”

Secor hopes that her research will allow a veterinarian or doctor to take a small sample of joint fluid and confirm early arthritis with one of the biomarkers that she will identify. Then doctor and patient could put the brakes on the disease before it progresses too far.

Treatment Tailored to the Patient

When it comes to arthritis treatment, horses and humans are in the same boat: veterinarians and doctors rely on trial and error, trying one treatment and then another to learn which one best mitigates the patient’s symptoms. This lack of precision is frustrating for patients and doctors, and it can delay recovery.

Drawing on her clinical experience and her investigation of the body’s immune response during progressive stages of arthritis, Secor thinks that PTOA patients can be subdivided into clinically distinct categories based on the immune cell and protein populations in the patient’s diseased joints. If she can define those categories, physicians could apply a precision medicine approach, choosing the most useful treatment for each patient based on the patient’s disease category.

Secor is currently testing the effectiveness of anti-inflammatory steroids, lab-created lubricin (an important part of synovial fluid), and therapies derived from the patient’s own tissues, such as platelet-rich plasma.

Of her new student, Reesink says, “We are very excited about the work that Dr. Secor is pursuing. [She] brings a unique skill set to these projects as a veterinarian and board-certified equine surgeon, and we are hoping to employ immunology, transcriptomics, and imaging techniques to decipher how existing joint therapies and new potential therapies can be catered to the right patient for the right injury at the right time.”

Secor acknowledges the value of her clinical veterinary background. “Coming into my PhD with several years of private practice was really beneficial in how I view the global problem my research is looking at, but also my experimental methods,” she says.

When asked what keeps her coming back to Cornell, now for her third degree, Secor says, “There is a huge encouragement and push for collaboration among the departments on campus. We have partners in Biomedical Engineering that we meet with weekly to discuss project ideas and bounce experiments off of each other. You’re encouraged to reach out and extend beyond your comfort zones.” According to Secor, the tools and expertise at Cornell, with its world-renowned veterinary and medical schools, make it the best place for the cross-disciplinary research that she is pursuing.

Considering Secor’s passion for her research, personalized treatments for arthritis may be here soon.

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