Publications

Society for Investigative Dermatology (SID) | April 26 - 29, 2017
Portland, OR

  • Small Molecule Wnt Pathway Inhibitor (SM04755) as a Potential Topical Psoriasis Treatment
    Abstract - Poster

American College of Rheumatology (ACR) | November 11 - 16, 2016
Washington D.C.

  • Discovery of a Small Molecule Inhibitor of the Wnt Pathway (SM04755) As a Potential Topical Treatment for Psoriasis
    Abstract - Poster

Overview: Psoriasis

Psoriasis is the most common chronic, immune-mediated skin disorder, affecting up to approximately 3% of the US population, varying by family history, race, and geographic location.1

  • Plaque psoriasis, the most prevalent type, is characterized by thickened epidermal layers resulting from the abnormal growth, differentiation, and apoptosis (cell death) of keratinocytes, producing raised, well-demarcated, erythematous, and frequently pruritic/painful plaques with silvery scales.
  • In addition to the physical and psychological impact of disease, psoriasis is associated with specific comorbidities, including psoriatic arthritis, obesity, diabetes, cardiovascular disease, metabolic syndrome and inflammatory bowel disease.2
  • Current treatment is determined by disease severity, which is generally established by the body surface area involvement.
  • While mild disease can be treated with topical therapy, moderate to severe disease frequently requires systemic medications, such as biologic agents.

The Wnt signaling pathway has been shown to play an essential role in the self-renewal and proliferation of keratinocytes.3

  • Studies in patients with psoriasis have shown that Wnt protein expression is increased, and inhibitory proteins are decreased in biopsies of psoriatic lesions.
  • This indicates that there is increased Wnt signaling, and a reduction of intrinsic factors that moderate Wnt signaling involved in the disease process.4,5
  • Results from a recent study using samples from psoriatic lesions suggested that inhibition of a Wnt protein lead to a reduction in keratinocyte proliferation and induced apoptosis.6 These lines of evidence suggest that targeted Wnt inhibition is a potential therapeutic option for patients with plaque psoriasis.

References

    1. Mrowietz U, Elder J, Barker J. The importance of disease associations and concomitant therapy for the long-term management of psoriasis patients. Arch Dermatol Res. 2006;298:309-19.
    2. Sterry W, Barker J, Boehncke WH, et al. Biological therapies in the systemic management of psoriasis: International Consensus Conference. Br J Dermatol. 2004;151(Suppl 69):3-17.
    3. Widelitz R. Wnt signaling in skin organogenesis. Organogenesis. 2008;4:123-33.
    4. Reischl J, Schwenke S, Beekman J. Increased expression of Wnt5A in psoriatic plaques. J Invest Dermatol. 2007;127-9.
    5. Gudjonsson, JE, Johnston A, Stoll SW, et al. Evidence for altered Wnt signaling in psoriatic skin. J Invest Dermatol. 2010;130(7):1849-59.
    6. Zhang Y, Tu C, Zhang D, et al. Wnt/β-Catenin and Wnt5a/Ca2+ pathways regulate proliferation and apoptosis of keratinocytes in Psoriasis lesions. Cell Physiol Biochem. 2015;36:1890-1902.