Chances are you haven’t heard of COPA syndrome. That’s because it wasn’t identified as a form of arthritis until 2015. So, what is COPA syndrome? It is a rare, inherited autoimmune disease that is caused by mutation of the COPA gene. It usually appears in early childhood. Patients show symptoms of severe lung disease and arthritis.
Dr. Jordan Orange was one member of a large research team that first identified COPA syndrome in 2015. The team’s published work in Nature Genetics won the Arthritis Foundation’s 2015 Howley Award prize for significantly advancing the understanding of an arthritis-related disease.
Dr. Orange’s 3-year Arthritis Foundation-funded project “Targeting of Cellular Stress Points and Immune Priming to Relieve Symptoms Associated with COPA Syndrome” is working on the next steps to understand this disease. He hopes that what they learn will have broader applications to other forms of autoimmune arthritis.
The research team begins with what is already known about the genetics of the disease. The COPA gene codes for a protein called “coatomer subunit alpha” which is involved in transport of proteins made by the cell to locations where they are used. Mutations in the gene cause protein transport to be disrupted and stress to build within the cell. According to Dr. Orange, “In healthy cells, the body can sense stress in overworked or infected cells. Once stress is sensed, the cell usually tries to heal itself or begins the process of programmed cell death that allows for the development of newer healthy cells. But in forms of autoimmune arthritis like COPA syndrome, the excess stress continues to build and triggers an autoimmune response.”
The team wants to understand more about the cellular biology of COPA syndrome and find ways to interfere with the abnormal biology that triggers the autoimmune response. To do that, they are looking at how certain drugs (that are FDA-approved for other diseases) may change the pathways that lead to the buildup of cellular stress and return cell processes back to normal. They are using knowledge gained from treating cells in the lab to eventually developing a mouse model to better understand the biology of the development of COPA syndrome and other forms of autoimmune arthritis, with the ultimate goal of finding ways to change the cellular pathways that lead to disease.
“Even though this is an inherited disease, not everyone with the mutated COPA gene develops it,” Dr. Orange explained. “We don’t know why someone develops this disease at age 2 and someone else develops it at age 26. Some never develop it at all. Something triggers it. Do the same triggers work for other forms of autoimmune arthritis? Maybe. We’re hoping that by developing the mouse model to study this disease, we will find answers to these and other important questions that have broad applications to other forms of arthritis.”
So how did Dr. Orange and his team become interested in studying COPA syndrome? Dr. Levi Watkin, a co-investigator on the team, said that they didn’t go looking for COPA syndrome – it found them. “Seeing two families with the same rare disease presentations was very unusual. It led to questions like ‘What is it? What is wrong immunologically?’ Finding the answers to these questions after seeing the impact on the families drove us to dig deeper,” he said.
“Making a discovery that is relevant to a person is the most rewarding part of this work. We are committed to helping these families find answers,” Dr. Orange added.
Dr. Orange is the chief of Immunology, Allergy, and Rheumatology, professor and section head for Immunology, Allergy and Rheumatology in the department of Pediatrics at Baylor College of Medicine, and the director of the Center for Human Immunobiology at Texas Children’s Hospital. Dr. Watkin is an instructor in the department of Pediatrics – Immunology, Allergy and Rheumatology at Baylor College of Medicine.
- Researchers on the Path to a Cure – Spotlight on Dr. Nora Singer
- Researchers on the Path to a Cure – Spotlight on Dr. Richard F. Loeser, Jr
- Researchers on the Path to a Cure – Spotlight on Dr. Hongsik Cho
- Researchers on the Path to a Cure – Spotlight on Dr. Christine Beeton