New York, NY—January 10, 2018
Scleroderma is a terribly debilitating disease with no effective treatments and the mortality rates are still upwards of 20%-50%, the highest of any rheumatic disease.
This disabling autoimmune disorder results in inflammation and fibrosis leading to the thickening of the body’s connective tissue, including the skin; and for decades its treatment has been symptomatic and, at best, inconsistently effective. But new research by a team from Hospital for Special Surgery (HSS) in New York City may signal hope for patients suffering from the condition.
The mechanism behind systemic sclerosis is not well understood. However, new research published today in Science Translational Medicine reveals a potential breakthrough into the cause of this disease, and also provides a possible treatment lead. Led by HSS researcher Dr. Franck Barrat -- the Michael Bloomberg Chair and Senior Scientist at HSS – along with clinicians of the Scleroderma center of HSS, the work implicates what are called plasmacytoid dendritic cells (pDCs) in contributing to scleroderma.
Normally pDCs secrete a compound called interferon to help fight off infections. However, as Dr. Barrat’s study revealed, in scleroderma patients these cells are chronically activated and infiltrate the skin causing fibrosis and inflammation.
"Plasmacytoid dendritic cells are known to be activated in many other rheumatic conditions, including lupus," explains Dr. Barrat. "But our findings suggest that they participate in both establishing and maintaining fibrosis in the skin as well. This is a very interesting finding as it opens new ways to tackle this condition."
Dr. Barrat found that depleting pDCs in an animal model of scleroderma prevented the disease from forming, while also reversing already existing fibrosis.
The new research also revealed that a receptor on the surface of pDCs called TLR8 is responsible for their increased activity.
Dr. Barrat fully acknowledges the limitations of the new study in particular the part where the research used animal models of scleroderma, which only partially reflect the complexity of the disease in humans. But he’s hopeful that not only will the new findings help illuminate the pathology of a puzzling disease, they may also represent potential novel approaches to treatment.
Strategies to eliminate pDCs are currently being evaluated by drug companies in diseases other than scleroderma. And though these potential treatments are still years away from being available, Dr. Barrat hopes that "a better understanding of the role pDCs play in fibrosis will open up the possibility of repurposing existing drugs to treat patients with scleroderma".
About HSS | Hospital for Special Surgery
HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the eighth consecutive year) and No. 3 in rheumatology by U.S. News & World Report (2017-2018). Founded in 1863, the Hospital has one of the lowest infection rates in the country and was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center four consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State. In 2017 HSS provided care to 135,000 patients from 80 countries and performed more than 32,000 surgical procedures. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. The HSS Innovation Institute was formed in 2015 to realize the potential of new drugs, therapeutics and devices; the global standard total knee replacement was developed at HSS in 1969, and in 2017 HSS made 130 invention submissions (more than 2x the submissions in 2015). The HSS Education Institute provides continuing medical curriculum to more than 15,000 subscribing musculoskeletal healthcare professionals in 110 countries. Through HSS Global, the institution is collaborating with medical centers worldwide to advance the quality and value of care and to make world-class HSS care more accessible to more people.