Small Molecule Wnt Pathway Inhibitor (SM04755) as a Potential Topical Psoriasis Treatment

In a study from 2017, SM04755, a small-molecule inhibitor of the Wnt signaling pathway, showed promise as a topical treatment for psoriasis. It effectively inhibited Wnt signaling, reduced pro-inflammatory cytokine secretion in monocytes and PBMCs, and curbed cytokine-induced keratinocyte proliferation. Additionally, it decreased fibrosis markers in human dermal fibroblasts. In a mouse model of psoriasis, SM04755 improved skin health, reduced skin and ear thickness, and decreased spleen weight, all with statistical significance compared to a control. While the positive control, clobetasol, reduced skin thickness more effectively, it also caused thinning below normal levels, suggesting an adverse effect. SM04755 also inhibited T cell activation and cytokine secretion ex vivo, further supporting its potential as a psoriasis treatment.