A recent study of four patients with disabling pansclerotic morphea has revealed they share an overactive version of a protein called STAT4.
Disabling pansclerotic morphea is a very rare disease characterized by severe skin lesions and poor wound healing which leads to deep scarring of all layers of the skin and muscle. The muscles eventually harden and break down causing the joints to stiffen which in turn leads to reduced mobility. Existing treatments help to halt the progression of the disease with many having severe side effects.
This new study, led by researchers from the National Human Genome Research Institute (NHGRI), part of the National Institute of Health (NIH), was carried out in collaboration with researchers from the University of California, San Diego and the University of Pittsburgh, as well as the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Allergy and Infectious Diseases, both of which form part of NIH.
During the study, researchers used genome sequencing to study four patients with the disease and discovered that all four had genomic variants in the STAT4 gene, a protein that plays a role in fighting infection and controlling important aspects of wound-healing. They found that the variant resulted in an overactive STAT4 protein, creating a positive feedback loop of inflammation for these patients. This caused impairment of their wound-healing that worsened over time.
In an effort to stop this feedback loop, researchers treated the patients with a Janus kinase (JAK) inhibitor, ruxolitinib, to target another protein in the inflammatory pathway. They found that upon treatment, the patients’ rashes and ulcers dramatically improved.
According to Sarah Blackstone, a predoctoral fellow within NHGRI’s Inflammatory Disease Section, a medical student at the University of South Dakota, and co-first author of the study, “Researchers previously thought that this disorder was caused by the immune system attacking the skin. However, we found that this is an oversimplification, and that both skin and the immune system play an active role in disabling pansclerotic morphea.” She continued by stating, “So far, there has not been a standard treatment for this disorder because it’s so rare and not well understood. However, our study gives an important new treatment option for these patients.”