Author Interviews, Dermatology / 22.03.2015

MedicalResearch.com Interview with: Nicolette Farman MD Ph.D. Directeur de recherche Université Pierre et Marie Curie, Paris, France Centre de Recherche des Cordeliers Paris, France Medical Research: What is the background for this study? What are the main findings? Dr. Farman: I have been working for a long time on aldosterone, a steroid hormone that enhances renal sodium transport, thus regulating blood pressure levels. Importantly, excessive effects of the hormone can be blocked by a pharmacological agent (a blocker of the receptor of the hormone): spironolactone. This drug has been used for decades as an anti-hypertensive drug. We identified several tissues where the receptor for the hormone (the mineralocorticoid receptor, MR) is expressed, in addition to kidney cells. Unexpectedly we found the receptor to be present in the human epidermis, but its role there was ignored. We designed first a mouse model, and found that overexpression of the receptor leads to thin and fragile skin in mice, as observed in glucocorticoid-treated skin. We hypothetized that perhaps the glucocorticoids exhibit this deleterious side-effect because they could bind to the mineralocorticoid receptor. As a consequence, we argued that pharmacological blockade of the MR over the skin should limit this side-effect. We used human skin explants in culture, and treated them with a potent dermocorticoid (clobetasol) alone or together with spironolactone. After 5 days in culture, we saw that spironolactone could indeed limit the atrophy of the epidermis induced by the dermocorticoid. Then a clinical trial was performed in healthy volunteers, that confirmed the efficiency of topical spironolactone to limit glucocorticoid-induced atrophy. Although the effect is not full reversion, the benefit was there. This is why we propose now that this approach could bring benefit to patients, if our results are confirmed in patients with psoriasis or eczema, that receive a dermocorticoid cream or gel. (more…)