De Novo Synthesis of Glucocorticoids in the Epidermis and Its Uses and Applications (Patent Application)

U.S. Patent Application No. 20080274079
Inventor: Marjana Tomic-Canic and Harold Brem
November 6, 2008

This patent is related to the discovery that epidermis is a steroidogenic tissue, which means that is produces and secretes a steroid, cortisol, completely independent of signals from other parts of the endocrine system, like the adrenal gland. Cortisol is part of a group of steroids known as glucocorticoids, which the epidermis produces during both its healthy state and its acutely wounded state. In the tissue of chronic wounds the glucocorticoid pathway, which modulates its synthesis and secretion, is erroneously activated. Dr. Brem and his collaborator Dr. Tomic-Canic found that the tissue of chronic wounds makes too much glucocorticoid because the enzyme that synthesizes it is over-expressed. Additionally, the receptor pathway is kept in a constant state of activation.

This discovery highlights an opportunity for clinical intervention; the over-production of glucocorticoid needs to be treated. This can be done with drugs that are antagonists or inhibitors of the pathway, which include the therapeutic drug RU486. Alternatively, a drug could be used that specifically targets the enzyme that synthesizes glucocorticoid, such as metyrapone. Another mechanistic option is to utilize a drug that stimulates the enzyme that converts active cortisol into inactive cortisone. This would achieve an overall decrease in the active form of the drug, without necessarily affecting the entire glucocorticoid pathway.

These findings have important implications for the prevention and treatment of inflammatory conditions of the skin, including acute wounds and, importantly, chronic non-healing wounds.

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