Effect of Topical PPARβ/δ and PPARγ Agonists on Plaque Psoriasis

Abstract

BACKGROUND: Ligands of nuclear hormone receptors such as glucocorticoid, retinoid and vitamin D are useful antipsoriatic drugs. Peroxisome proliferator-activated receptors (PPARs), which also belong to the nuclear hormone receptor superfamily, are pleiotropic regulators of growth and differentiation in many cell types, including the keratinocytes. Recent reports have dealt with the involvement of PPARalpha in epidermal processes such as barrier development, proliferation and differentiation. In a pilot study of topical clofibrate, a PPARalpha ligand, we did not find any antipsoriatic activity. No study on the effect of topical application of other PPAR subtype ligands (PPARbeta/delta and gamma) has been published. OBJECTIVES: The purpose of this pilot study is to explore the clinical efficacy of the topical application of potent PPARbeta/delta and gamma agonists on plaque psoriasis, tetradecylthioacetic acid (TTA) and rosiglitazone, respectively. METHODS: In a pilot study on psoriatic patients, 8 individuals (5 male/3 female) were treated twice daily for 30 days with vehicle (n = 14 plaques), rosiglitazone 0.5% (n = 18) and TTA 0.5% (n = 18). Assessments of the PASI plaque score were carried out on days 0, 4, 7, 11, 14 and 30. RESULTS: No statistically significant difference was found at any of the examination times, between vehicle, rosiglitazone and TTA in terms of reduction of the PASI plaque score for total, scale and infiltration scores. Treatments were well tolerated, and skin irritation, adverse drug-related symptoms and dropouts did not occur. CONCLUSIONS: With the reservations due to the limited nature of this pilot trial, it seems that these topical PPARbeta/delta and gamma agonists do not exert a strong antipsoriatic effect when used alone at 0.5%.