Dersimelegon: A Promising MC1R Agonist for Systemic Sclerosis Therapy

The study explores the role of melanocortin 1 receptor (MC1R) activation in combating skin fibrosis, a characteristic of systemic sclerosis (SSc). The research focuses on MT-7117, a drug candidate that acts as an MC1R agonist. The drug was tested in mice with SSc-like symptoms induced by bleomycin (BLM), and its effects on fibrosis and inflammation were measured. The study also examined MC1R's presence in the skin of SSc patients.

MT-7117 was found to be effective in reducing skin collagen levels, serum protein D levels, and lung weight in the BLM-induced model when administered prophylactically. Therapeutic administration of the drug also reduced skin thickening and myofibroblast counts. Gene expression analysis indicated that MT-7117 influences categories related to immune cells and endothelial cells, as well as biological functions and molecular pathways linked to inflammation and fibrosis.

Serum protein profiling showed that MT-7117 reduced levels of several SSc-related biomarkers. In vitro tests revealed that the drug inhibits the activation of human dermal fibroblasts by suppressing TGF-β-induced gene expression. Immunohistochemical analysis confirmed MC1R's presence in various skin components of SSc patients.

The findings suggest that MT-7117 has the potential to be a therapeutic agent for SSc by targeting inflammation, vascular dysfunction, and fibrosis. A phase 2 clinical trial is underway to assess the drug's efficacy and safety in early-stage SSc patients.