MedicalResearch.com Interview with:
Nicolette Farman MD Ph.D.
Directeur de recherche
Université Pierre et Marie Curie, Paris, France
Centre de Recherche des Cordeliers
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.
Medical Research: What should clinicians and patients take away from your report?
Dr. Farman: Our study is a first step; it is too early to use spironolactone now
to treat epidermal atrophy. We need to expand our knowledge with
inclusion of subjects with skin diseases (psoriasis or eczema) to
evaluate the benefit of adding spironolactone on top of the classical
glucocorticoid treatment, in well defined and controlled conditions
(new clinical trials). It will be also necessary to reformulate
spironolactone for cutaneous use, including toxicology and
pharmacodynamic studies. It is only after these mandatory steps that
clinical use of a spironolactone cream will be proposed, and with
limited specific applications in human diseases.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Farman: Future research should identify the cellular mechanisms at the origin
of this potential benefit (fundamental research) and try to identify
those patients that should successfully benefit from this treatment.
Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in human Skin.
Maubec E1, Laouénan C2, Deschamps L3, Nguyen VT4, Scheer-Senyarich I5, Wackenheim-Jacobs AC6, Steff M1, Duhamel S7, Tubiana S8, Brahimi N5, Leclerc-Mercier S9, Crickx B1, Perret C7, Aractingi S10, Escoubet B11, Duval X8, Arnaud P12, Jaisser F7, Mentré F2, Farman N7.
MedicalResearch.com Interview with: Nicolette Farman MD Ph.D. (2015). Topical Spironolactone May Limit Skin Thinning From Steroids