Project: Age Related Skin Disorders : development of a new treatment candidate and a new method to analyse treatments efficacy

The skin is the largest organ of the body and has a very complex and heterogeneous structure. It has a large number of important functions, the most important being to provide a barrier between the body and the external environment. To provide this permeability barrier, keratinocytes undergo a complex pathway of differentiation, which culminates in keratinocyte cornification and the formation of extracellular lipid-enriched lamellar membranes in the stratum corneum (Fiengold KR, J Lipid Res 2009: 50: S417-S422). The extracellular lamellar membranes are derived from the exocytosis of lamellar bodies and to synthesize such lamellar bodies, the keratinocytes need abundant quantities of cholesterol, fatty acids and ceramides. These lipids also could serve as signaling molecules and thereby coordinately regulate the formation of the stratum corneum (Fiengold KR, J Invest Dermatol 2012: 132: 1951-1943)._x000D__x000D_The skin physiological changes that occur over time lead to a lack in neutral lipid synthesis and thus to an impaired epidermal barrier repair. This phenomenon is known as chronological aging. Contrary to photo-aging that occurs due to some environmental aggressors (such as UV radiation), there is no prescription treatment for chronological aging to date. _x000D_Moreover, defect in these lipids metabolism, results in altered permeability barrier function establishment and increases the risk of developing xerosis/dry skin, or, more problematic, inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (Scharschmidt TC et al., J Allergy Clin Immunol 2009: 124: 496–506). In addition to defects in permeability barrier function leading to skin dryness, these skin diseases are characterized by a spectrum of abnormalities, including inflammation, and abnormal keratinocyte terminal differentiation following alteration in gene expression of several specific markers involved in the skin's homeostasis (Schmuth M et al., J lipid Res 2008: 49:499-509; Cork MJ et al., J Invest Dermatol 2009: 129:1892-1908). Because dermatitis affects about 5% of the general population and up to 20% of children, and because treatments currently available are inconclusive, strategies to study and treat this skin disorder are of great interest._x000D_A lot has to be done in this purpose since studies of lipid metabolism in the epidermis have not been in the COstream of lipid research._x000D_The skin is a very important site of lipid synthesis, therefore, it is not surprising that nuclear hormone receptors, known as key players in lipid homeostatis and being activated by endogenous lipids (liposensors), are present in the skin and regulate a wide variety of skin functions (Schmuth M et al., J lipid Res 2008: 49:499-509). _x000D_Dendrogenins are original alkylamino-oxysterols that are potent inductors of cell differentiation (de Medina P et al., J Med Chem 2009 : 52 : 7765-7777, de Medina et al., Nature Comm. in press). Members of this family of compounds are promising drug candidates for treatment of cancers and degenerative diseases such as deafness (Fransson et al., submitted). From this family, a derivative (AF130) showed potency to stimulate important mechanisms involved in physiological differentiation and taning processes (Affichem, unpublished results)._x000D_In this context, we hypothesized that this Dendrogenin could interfere with various steps involved not only in skin aging but also in melanogenesis. _x000D_The aim of ARSkinD project is to develop a new active ingredient stimulating the CO key steps of differentiation-related effects on keratinocytes and an original new technique to evaluate in depth potency to prevent or treat skin aging, to be used for preclinical evaluation of new candidates to answer this unmet need._x000D__x000D_The program will be based on a mutual exchange of experience between two SMEs to reach the market with two commercial offers, one dermocosmetic ingredient and one unique R&D offer. For this purpose, Affichem will contribute by providing the active ingredient, the knowledge and know-how about lipidology and liquid chromatography. StratiCELL will contribute by providing expertise in the field of cosmetology and technical platform for validation of cosmetics prior to assays in human. The two Ps thus have all knowledge and know-how needed to complete studies planned in ARSkinD projet.

Acronym ARSkinD (Reference Number: 8571)
Duration 01/09/2013 - 28/02/2016
Project Topic Ps of the project plan to develop a new treatment to address topic diseases related to skin aging and an original new method to assess potency of new therapies developed to treat and/or prevent such diseases
Network Eurostars
Call Eurostars Cut-Off 10

Project partner

Number Name Role Country
2 Affichem SA Coordinator France
2 StratiCELL Screening Technologies SA Partner Belgium