Samumed, a pharmaceutical company focused on regenerative medicine and oncology applications, is encouraged by the results and expects to expand its ongoing clinical trials testing SM04755 for other diseases.
Results were presented at the 2016 American College of Rheumatology (ACR) Annual Meeting Nov. 11-16 in a poster presentation titled “Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04755) As a Potential Topical Treatment for Scleroderma.”
The Wnt pathway regulates key processes inside cells and plays an important role in inflammation, skin fibrosis, and vasculopathy (a disease affecting blood vessels). Earlier studies showed that Wnt signaling is up-regulated in scleroderma, and its increase promotes differentiation of fibroblasts into myofibroblasts and the secretion of extracellular matrix proteins, thereby promoting fibrosis and dermal thickening.
In this study, researchers tested SM04755 in vitro and found that this small molecule inhibited inflammation and reversed dermal fibrosis. The team tested SM04755 anti-inflammatory activity by measuring the levels of important inflammatory cytokines, including IL-6 and TNF-alpha. They observed that SM04755 significantly inhibited the secretion of both cytokines.
SM04755 also prevented and reversed fibrosis in vitro, as shown by a decrease in several fibrosis mediators, including smooth muscle actin (αSMA), plasminogen activator inhibitor, connective tissue growth factor, and collagen expression.
Researchers also conducted in vivo studies using a scleroderma mouse model (the bleomycin scleroderma model). They observed that topical application of SM04755 (meaning it is applied on the skin or mucous membranes) reversed dermal fibrosis, increased adipose tissue (fat) thickness, and reduced vasculopathy when compared to controls. These results were achieved with minimal exposure to toxic effects both locally and systemically.
The results highlight the therapeutic potential of SM04755 as a topical therapy for scleroderma.
“Based on our study results, we are excited about SM04755’s potential as a treatment for scleroderma,” Yusuf Yazici, MD, chief medical officer of Samumed, said in a press release. “We expect to expand our ongoing clinical trials for SM04755 from chronic tendinopathy to psoriasis and scleroderma in 2017.”