Treating Rheumatoid Arthritis – A Challenge

Treating Rheumatoid Arthritis – A Challenge

Dr Noss is an assistant professor, division of rheumatology, Roosevelt Clinic, University Washington Medical Center. Dr Noss received her MD as well as her PhD in 2002 from Case Western Reserve University. She completed her residency in internal medicine in 2004 and her fellowship in rheumatology in 2008, both at Brigham and Women’s hospital, Boston.

Trial and Error

Despite the improvements in RA treatment that have been made in the last two decades there are still sizeable challenges facing rheumatologists today, particularly relating to selection of treatment option for their patients. Striving to treat patients, these difficulties come to the fore for Dr Noss. “The hardest part about being a rheumatologist is starting patients on the right drug,” says Dr. Erika Noss, a physician-scientist at the University of Washington Medical Center. “With rheumatoid arthritis (RA), all you can do is give it your best shot. You’re simply rolling the dice.”

In her career Dr Noss has experienced her patients facing many hardships. One such patient, a social worker, underwent years of swollen joints, stiff knees and debilitating pain. Her work requiring home visits and travel around the city. This patient returned to the clinic time and again, looking for some form of relief. Each time a patient is put onto a new drug regime it requires three to four months to establish their effect. It’s a waiting game, and in this case, it took six attempts and many months to find a drug that offered her respite from her RA.

So how do the treating physicians choose the best drug for their patients? Unfortunately, there is no easy answer to this question. It is necessary to choose whether you’re going to target the T-cells, B-cells or one of the body’s inflammatory chemicals. One cannot simply keep changing or adding new drugs. There’s a limit to how many drugs people can take to suppress the immune system before chronic infections become a serious side effect.

Even with numerous new treatments, remission is not achievable for all patients. Around 80% of patients do find some level of relief after trying a number of different treatments. It is Dr Noss’ ambition to improve this percentage and offer relief to a greater number of patients.

The Role of Fibroblasts

Funding as an ANRF fellow and grant recipient has allowed Dr Noss to rigorously pursue this goal. This research is directed towards activated fibroblasts. Fibroblasts are biological cells key in the synthesis of the extracellular matrix and collagen, necessary in the structural framework of tissues and wound healing (tissue damage inducing the production of fibroblasts).

In patients with RA this system of cells is sent into overdrive. Fibroblasts are pumped out at an accelerated rate, clogging the joints, intensifying inflammation and destroying the cartilage that normally cushions the joints. As RA begins in the immune system it made sense to Dr Noss to search for potential new drugs that work at a cellular level. This led to a number of research questions – Is it possible to block these rogue fibroblasts? How do you reduce the associated risk of infection? Is there a way to combine drug therapies to target fibroblasts with current biologicals that block the immune system? “Maybe a cell that’s not traditionally a drug target, like a fibroblast, will someday put people completely into remission.”

Recent Observations

Dr. Noss’s most recent research focuses on the role of cadherins in fibroblasts. Cadherins are cell adhesion molecules that are important in the formation of adherens junctions, protein complexes, allowing cells to bind with one another. Cadherin 11 is a protein expressed in the cell lines responsible for bone formation (osteoblasts), it is upregulated during the differentiation of these cells, suggesting a specific function in bone development and maintenance. In studies published in Science and PNAS, Dr Noss showed that deficiency or blockade of cadherin 11 resulted in protection in mouse models of arthritis and also demonstrated that ligation of this adhesion molecule leads to induction of pro-inflammatory cytokines. Cadherin 11 is a marker and regulator of synovial fibroblast function in inflammatory arthritis. Unpacking the mechanisms behind this relationship may lead to new therapeutic targets that prevent long-term joint destruction resulting from RA. ANRF is proud to have contributed in a small way to these discoveries and strongly believes that a cure for arthritis will be found through the tireless work by researchers such as Dr Noss.

 


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ANRF
Article Author
Arthritis National Research Foundation
arthritisresearch@curearthritis.org

The Arthritis National Research Foundation's mission is to provide initial research funding to brilliant, investigative scientists with new ideas to cure arthritis and related autoimmune diseases. Writing articles about the patients affected and the science being done to find a cure shows why we need to come together to #CureArthritis!

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