Pursuing innovative treatment for Sjögren’s disease

McCoy runs one of two Sjögren’s clinics in the Midwest that serve patients from across the United States. Her pioneering research has led to greater understanding of the disease, as well as a new diagnostic tool and a clinical trial for an experimental treatment that she hopes will dramatically improve patients’ quality of life.

McCoy and her cross-disciplinary team received the 2022 WARF Innovation Award from the Wisconsin Alumni Research Association (WARF) for their innovative diagnostic test for Sjögren’s disease. WARF, which serve as the technology transfer office for UW–Madison, has supported faculty across the University of Wisconsin School of Medicine and Public Health through grants, research facilities, and the patenting and licensing of breakthroughs that have benefited the world.

How do you describe your field and specialty?

Rheumatology focuses on patients with diseases of the immune system, and within that field, I focus on Sjögren’s disease, a systemic immune disease. With Sjögren’s, patients’ immune systems attack the glands that make tears and saliva, leaving them with severe dryness. In a subset of patients, the immune system could attack other organs such as the lungs, as well as joints, peripheral nervous system and bone marrow.

How did you decide you wanted to study Sjögren’s?

When I came to UW, I realized that this was a group of patients with significant disease burden, yet there were no clear disease-modifying treatments available to them. This motivated me to use my bench and clinical skillset to meet two key goals: one, move our understanding of the disease forward so we could develop better diagnostic and treatment tools; and two, provide cutting-edge therapies to alleviate their daily symptom burden.

What are some of the day-to-day difficulties of living with this disease?    

We take talking, eating and crying for granted, but these actions pose huge challenges for many of my patients, limiting their day-to-day functionality and social interactions. It is hard to imagine the lack of something — try to envision a total lack of tears and saliva. My patients cannot cry when they are upset and must wake up throughout the night to place drops in their eyes. Sometimes they cannot see because they lack lubrication in their eyes. Dry mouth makes it difficult to perform simple tasks such as talking and eating.

How has scientific understanding of Sjögren’s progressed over the years?

In 1888, one of the first patients thought to have Sjögren’s was treated with Pilocarpus jaborandi, a plant native to South America. This is where modern pilocarpine, an ingredient in today’s over-the-counter wetting agents and other products used to treat dryness, originates. Such products have not changed significantly in over 100 years. For the first time, however, multiple clinical trials to evaluate new treatment options are meeting their Phase II endpoints — measurable outcomes that determine whether a new treatment is effective — providing hope that in the near future, we might identify therapies for subsets of Sjögren’s patients that could address the root cause of their symptoms.

Your team developed a new diagnostic tool for Sjögren’s. How was the idea sparked?

My patients are the inspiration for the research that I pursue at the bench. Although most Sjögren’s patients can be diagnosed with a simple blood test, one-third require a lip biopsy to confirm the presence of their disease. It can be very hard to find someone to do a lip biopsy. Furthermore, many patients have concerns about the procedure itself, which can be painful. The new diagnostic tool is a simple blood test that shows promise for being able to diagnose certain Sjögren’s patients without the need for a biopsy. I worked with a team of antibody, array technology, and biostatistical experts to understand how we might perform such a test. Now I am working with multiple national and international experts to further validate our results.

You described having a clinician’s “frustration” at not being able to help patients who are suffering with Sjögren’s. What role does this play in innovation?

We enter the field of medicine to make patients feel better. Unfortunately, in the case of Sjögren’s, we currently have limited options to help improve our patients’ quality of life and those interventions mostly treat the end results of having Sjögren’s, without addressing the root cause. My patients’ symptom burden helps motivate me at the bench to develop new therapies to address their needs.

How did you develop the idea to launch a clinical trial for stem cell therapy as a treatment for Sjögren’s?

Dr. Jacques Galipeau, a professor of hematology, oncology and palliative care within the Department of Medicine, gave a talk in 2017 about the work of the UW Program for Advanced Cell Therapy (PACT) and his past experience using mesenchymal stromal cell (MSC, a type of stem cell) therapy. I approached Dr. Galipeau with the concept of deploying MSC therapy to treat my patients — particularly ones who have lower activity of their immune system or chronic scarring on their salivary glands due to the disease. While some drugs to treat Sjögren’s appear promising in current clinical trials, they do not usually address those patient populations. I wondered if stem cells from the patient’s body could be used to improve the salivary glands’ function. Dr. Galipeau and I began collaborating to develop new therapeutic insights at the bench that ultimately culminated in this first-in-world trial of activated MSCs to treat Sjögren’s dryness.

After treating the first patient in the clinical trial, what are you most excited about?

This first successful treatment is motivational because our patient had an excellent response to therapy. That said, we must complete this first phase of the study focused on safety before we generate more data to confirm the efficacy of our therapy.

We hope to develop a therapy that focuses on Sjögren’s patients, as well as graft-versus-host disease patients, who also experience severe dry mouth. Our ultimate goal is to improve the quality of life of patients who suffer from dryness without effective therapeutic options.

A clinical trial can take a long time, with possible setbacks. As a researcher, how do you overcome discouragement and tap into persistence?

I believe that offering cutting-edge trials to patients is a critically important role for clinicians at major academic centers. We give our patients the opportunity to take an active role in their treatment and in scientific advancement. Clinical trials often experience delays and unanticipated barriers, but most of these challenges can be solved with hard work over time. I am confident this trial will proceed but, as always, I am prepared to tackle any challenges along the way toward deploying this therapy to a broader population of patients.

Why is UW–Madison a great place to be pursuing your research?

I must first credit the patients in my Sjögren’s clinic, each struggling with unique symptoms and burdens due to their disease. Their passion and interest in driving Sjögren’s research forward is inspiring. Also, the collaborative environment at UW is top notch. A conversation with Dr. Jacques Galipeau led to years of scientific collaboration that ultimately resulted in the initiation of our groundbreaking trial. We now have a diverse and talented collaborative team working to develop and deploy our novel cell therapies. UW’s vibrant academic environment fosters innovation that ultimately improves the lives of our patients.