Development of a Topical siRNA Therapy to Promote Burn Wound Healing via Depletion of the Novel Microtubule Regulatory Fidgetin Like

There are clinically treated burn wounds in the United States each year The recovery from these burn wounds involves prolonged healing that can take up to a year or more before there is complete tissue regeneration In many cases the burn victim is left with disfiguring scars Wound healing occurs in three distinct stages an initial inflammatory phase Phase a proliferative phase Phase and a long tissue remodeling phase Phase that restores the skin to the pre wound state As strategies for wound care have evolved from skin grafts and passive dressings to biopharmaceutical approaches most innovation has continued to promote only Phase either with new materials that better clean and protect the wounded tissue or with growth factors and or other factors that modulate the immune response These approaches are important for coaxing a wound to enter Phase but do little to for remodeling and repair of the tissue Phase Additionally excessive use of growth factor containing products has been found to increase lifetime cancer risk in patients Thus to improve patient outcomes there is a need for a safe and effective therapy that expedites both early stages of wound healing Phases and and results in a more efficiently closed and effectively matured wound Phase Fidgetin like FL is a recently discovered regulator of the microtubule cytoskeleton that severs and depolymerizes microtubules Down regulation of FL expression enhanced microtubule function to promote cell motility in vitro and improved healing both clinically and histologically in murine animal models MicroCures aims to develop a topical nanoparticle siRNA treatment to this novel target FL FL NP si to directly enhance the wound closure and dermal maturation function of fibroblasts and keratinocytes thereby addressing for the first time the challenge of accelerated healing and tissue repair in acute wounds Thus wound healing can occur more rapidly with high fidelity resulting in reduction in endured pain lower risk of infection shorter hospital stays and decreased scarring The goal for this proposed project is to characterize a standard formulation of FL NP si in terms of efficacy and safety in two animal models Yorkshire pig Specific Aim and Sprague Dawley rat Specific Aim in preparation for IND enabling studies Time to wound healing and histopathology at the wound site will be evaluated in both animal models In addition whole animal histopathology and the maximum tolerated dose will be determined in Specific Aim At the end of the project period we will show that FL NP si is both safe and efficacious for the treatment of burn wounds and is ready for IND enabling studies There are approximately clinically treated burn wounds in the United States each year which can take up to a year or more before complete tissue repair Wound healing occurs in three distinct stages an initial inflammatory phase Phase a proliferative phase Phase and a long tissue remodeling phase Phase that restores the skin to the pre wound state however most treatments only affect Phase or more recently Phase MicroCures Inc aims to develop a topical nanoparticle siRNA treatment directed to a novel target FL FL NP si to directly enhance the wound closure Phase and and dermal maturation Phase function of fibroblasts and keratinocytes thereby addressing for the first time the challenge of accelerated healing and tissue repair in acute wounds