Phototherapy, a familiar therapeutic treatment modality in dermatology, may be coming to rheumatology.
Early data suggest that sequestering dexamethasone inside red blood cells, then using tuned laser energy to release the drug, could be used in arthritis.
“We are taking established therapies for rheumatoid arthritis that may have systemic side effects and delivering them in a novel way,” said Teresa K. Tarrant, MD, Associate Professor in Medicine at Duke University School of Medicine, Durham, NC. “The idea is to activate the drug at a targeted site using wavelengths of light that penetrate deeply into tissue. This should limit systemic toxicity and at the same time deliver more focused, patient-directed therapy.”
Dr. Tarrant will discuss her ground-breaking research during the session Rheumatology Research Foundation: Arthritis Research Showcase from 2:30 – 4:00 pm Monday in Room W470b. This symposium highlights research supported by the Rheumatology Research Foundation. The program features RRF-funded investigators who will focus on three distinct and cutting-edge research topics selected on the basis of their scientific innovation and relevance to clinical practice.
Deborah Lenschow, MD, PhD, Associate Professor of Medicine at the Washington University School of Medicine, St. Louis, MO, will discuss her lab’s latest findings on the immune factors that regulate disease pathogenesis in the reemerging alpha virus chikungunya. New information on disease pathways is expected to help identify novel therapeutic targets.
Liana Fraenkel, MD, MPH, Professor of Medicine at Yale University, focuses on developing methods to measure patient preferences. Her findings point the way to a novel shared decision-making tool with direct applications to clinical practice.
Dr. Tarrant is adapting phototherapy to deliver one of the oldest therapeutics in RA—an alternative to injecting steroids directly into inflamed joints. Joint injection works, but is invasive, can be painful, requires an office visit, and has limited duration of action. Systemic steroids can also be effective in RA, but the doses needed can induce a variety of adverse events, including cataract formation, hypertension, diabetes, and osteoporosis. Dr. Tarrant’s model attempts to circumnavigate these therapeutic challenges through sequestering dexamethasone inside circulating red blood cells (RBCs). Inside RBCs, the drug is bound to vitamin B12, which is linked to an antenna molecule that is sensitive to a specific wavelength of laser light. Circulation carries the drug-laden red blood cells to the inflamed joint and the rest of the body, but there is no drug exposure as long as the agent remains bound inside the RBCs.
“We will be applying this laser to the affected joint where blood is circulating through the synovium,” Dr. Tarrant said. “When you cleave the vitamin B12 link with laser light, the bound dexamethasone becomes membrane permeable and passes outside the red blood cell at that specific location… If we can activate drug release locally, we will not have the same degree of systemic toxicity.”
There is also the potential for patient-directed therapy in the future. Because drug is released only in tissues that are illuminated with the proper light frequency, patients could shine a laser activator directly on their painful joints at home. That avoids the need to inject the joint and could allow for repeated treatments.
The phototherapy delivery system works in human cell culture and in mouse ear models. The next step is proof of concept in a rodent model of RA.
“The Rheumatology Research Foundation is the number one foundation in the country that supports research, training and education in our field,” Dr. Tarrant said. “The RFF-supported research the three of us will be presenting could change the way we all treat our patients in the future.”