In a study of a very small population—four patients—with the rare disorder disabling pansclerotic morphea, researchers found that treatment with the oral Janus kinase (JAK) inhibitor ruxolitinib reduced disease activity and led to improvements in the patients’ ulcers and rashes. These findings were published by Baghdassarian et al in The New England Journal of Medicine. The investigators also discovered all four participants in the study had mutations in the STAT4 gene, which led them to target the STAT pathway with ruxolitinib, as JAK-STAT signaling is linked and the mutations seemed to be dependent on JAK activity. The researchers highlighted that their discovery of the STAT4 mutations in this population “appears to be the first description of a gain-of-function variant in this gene and the first genetic link for disabling pansclerotic morphea.”
In a companion press release on the findings issued by the National Institutes of Health, senior study author Dan Kastner, MD, PhD, Head of the National Human Genome Research Institute’s Inflammatory Disease Section and a distinguished investigator at the NIH, commented, “The findings of this study open doors for JAK inhibitors to be a potential treatment for other inflammatory skin disorders or disorders related to tissue scarring, whether it is scarring of the lungs, liver, or bone marrow.”