Wound Healing Properties of a Non-Irritating Novel 9-cis Retinoid Acid Derivative

DESCRIPTION (provided by applicant): MDI 301 is a synthetic retinoid that is similar to all-trans retinoic acid (RA) in its ability to stimulate collagen synthesis and inhibit the major collagen-degrading enzymes in skin. A major feature that distinguishes MDI 301 from RA is its lack of irritation when applied topically to skin. Recent studies from our laboratory have shown that topical treatment of diabetic rats with RA improves the healing of subsequently-induced abrasion wounds. Based on this, we have proposed the prophylactic use of RA as a way to improve structure/function in diabetic skin at risk for ulcer formation. A potential drawback to this strategy is skin irritation. If retinoid use in diabetic skin provokes irritation, this could result in non-use (as is does in other groups of retinoid users). Additionally, if the degree of irritation is too great, the irritation could counter-act the beneficial effects of retinoid treatment in the at-risk skin. The overall goal of the proposed studies is to determine if topical pretreatment of skin with MDI 301 will, like RA itself, improve healing of subsequently-induced wounds but do so without provoking irritation. If it can be shown that MDI 301 is as effective as RA without the negative consequence seen with RA use, it will provide a better agent for development as a chronic wound preventative. To achieve our overall goal, we will compare the effects of topical MDI 301 treatment with topical RA on dermal structure/function in streptozotocin diabetic (STZ-D) rats and compare healing of abrasion wounds in control rats, STZ-D rats and STZ-D rats that have been pretreated with topical RA or topical MDI 301.