Topical Scleroderma Medicine Seen to Lessen Fibrosis and Inflammation in Mouse Model

A new topical medicine, called SM04755, significantly decreased and even reversed fibrosis and inflammation in in vitro and in vivo mouse studies of scleroderma. These results suggest SM04755 is a potential topical medicine for scleroderma patients.

The study, “Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04755) As a Potential Topical Treatment for Scleroderma” will be presented at the 2016 American College of Rheumatology (ACR) Annual Meeting taking place in Washington, D.C., on Nov. 11–16.

The Wnt signaling pathway constitutes a key regulator of many cellular processes, with important roles in inflammation, skin fibrosis, and blood vessels disease (vasculopathy), and, not surprisingly, it is hyper-activated in scleroderma.

Researchers performed a series of preclinical studies to investigate the effects of a novel small-molecule that is a Wnt pathway inhibitor, the SM04755, in several aspects of scleroderma: inflammation, dermal fibrosis, and vasculopathy.

To this end, they measured Wnt pathway inhibition by SM04755, and its anti-inflammatory activity, effect on fibrosis, and how it impacts myofibroblast differentiation (a key step contributing to fibrosis in scleroderma) and reversion. Researchers also measured the drug’s in vivo efficacy, testing it in a bleomycin-induced mouse model of scleroderma.

The team observed that SM04755 demonstrated potent and selective inhibition of Wnt signaling. Moreover, it showed anti-inflammatory activity (demonstrated by the reduced expression of key inflammatory markers) in two types of cell lines,  THP-1 and peripheral blood mononuclear cells (PBMCs). SM04755 treatment significantly inhibited dermal fibrosis, and was even capable of reversing the fibrotic phenotype.

SM04755 is a topical drug (meaning it is used locally, being applied on the area in need of treatment), and topical application to the scleroderma mice significantly reversed the induced dermal fibrosis. SM04755 treatment also lowered vasculopathy when compared to controls.

These effects were achieved with minimal toxic exposure. Altogether, the findings support SM04755 as a potential topical therapy for scleroderma.

SM04755 is being developed by Samumed, a pharmaceutical company working in tissue regeneration.

Yusuf Yazici, MD, chief medical officer of Samumed, said in a press release, “We are excited to return to the ACR Annual Meeting with seven presentations that highlight the progress we’ve made in five disease areas with two of our small-molecule compounds, SM04755 and SM04690.”

Those five areas are scleroderma, chronic tendinopathy, psoriasis, osteoarthritis, and degenerative disc disease.