Topical drug effects on normal and proliferating epidermal cell models

Area of Science:

• Dermatology
• Pharmacology
• Skin Biology

Background:

• Antiproliferative agents are crucial for treating hyperproliferative skin conditions like psoriasis.
• Evaluating the efficacy of topical treatments in preclinical models is essential for clinical translation.
• Hairless mouse models offer a platform for studying skin responses to topical agents.

Purpose of the Study:

• To assess the predictive value of two hairless mouse models for topical antiproliferative drug efficacy in psoriasis.
• To compare the effects of 28 topical antiproliferative agents on normal and hyperproliferative mouse skin with human clinical responses.

Main Methods:

• Induction of epidermal hyperproliferation in hairless mice using an essential fatty acid-deficient diet or short-wavelength ultraviolet (UV) irradiation.
• Topical application of 28 antiproliferative agents to mouse skin.
• Measurement of epidermal DNA synthesis using hydroxyapatite column chromatography.
• Comparison of mouse model responses with clinical outcomes in psoriasis patients.

Main Results:

• The essential fatty acid-deficient diet-induced hyperproliferation mouse model demonstrated a good correlation with clinical responses in psoriasis patients for most tested drugs.
• The UV-induced hyperproliferation mouse model showed a poorer correlation with clinical outcomes.
• Variations in epidermal DNA synthetic rates in the UV model may explain the reduced clinical correlation.

Conclusions:

• The essential fatty acid-deficient diet hairless mouse model serves as a valuable predictive tool for topical antiproliferative drug efficacy in psoriasis.
• The UV-induced model requires further refinement to improve its predictive accuracy for topical psoriasis treatments.