We use reconstructed human epidermis to model the skin disorders we are targeting such as ichthyosis and Darier disease. We use cells from patient suffering from these diseases in order to study the effect of our compounds on the structure of the epidermis and the impact on gene and protein expression and, om skin barrier. These models showed histological features similar to those observed in in vivo human skin. We also use this model to assess the toxicity of our new small molecules.

Darier Disease RHE

Healthy RHE

Lamellar Ichthyosis RHE

Biosynthesis and metabolism of Retinoic Acid in the skin:

1) Dietary carotene and retinol (vitamin A) are processed by different enzymes to provide endogenous Retinoic Acid;

2) Retinoic Acid is metabolized (transformed) to biologically inactive Retinoic Acid derivatives by an enzyme named CYP26.

3) These molecules have lost the biological properties of Retinoic Acid. When Retinoic Acid is metabolized, it cannot induce the desired biological effects necessary to treat skin disorders.

At DermaXon we are selectively increasing the concentration of endogenous retinoic acid in the skin, efficiently treat ichthyosis and Darier disease by reducing inflammation and regulating abnormal keratinization. Because of their high selectivity for their biological target, adverse effects related to the use of Dermaxon’s compounds are expected to be dramatically reduced or non-existent compared to those reported for approved topical acne treatments.