A Novel Therapeutic that Harnesses MIcrotubules to Enhance Corneal Wound Healing Following an Alkaline Burn

The cornea is one of the most important tissues in the eye and its transparency is critical for good visual function in humansCorneal tissue injuries are the most common everyday issue for practicing ophthalmologists and can run the gamut in severityIn severe modelssuch as corneal alkaline burnsextensive healing is needed and often the burn victim is left with reduced visual acuityHealing of large corneal woundssuch as alkali burnsinvolves extended migration of epithelial cellsHowevercomplications from injury induced inflammation slows epithelial migration and worsens outcomesThe inability to seal the corneal epithelium results in persisting inflammation and increases the risk for corneal ulcerationAs strategies for wound care have evolvedmost innovation has continued to focus on minimizing inflammationThese approaches are important for coaxing cells to migrate and heal the corneal epitheliumbut do little for remodeling and repair of the tissueresulting in weakly attached tissue and slow healingThusto improve patient outcomes there is a need for a safe and effective therapy that both expedites migration soon after injury and results in a more efficiently closed and effectively matured woundIdeallymechanisms that deliver factors to enhance corneal wound healing would be safeapplied topicallyremain localized at the site of applicationand provide a rapid but sustained release of the active reagentFidgetin likeFLis a recently discovered regulator of the microtubule cytoskeleton that severs and depolymerizes microtubulesDown regulation of FLexpression enhanced microtubule function to promote cell motility in vitro and improved healing both clinically and histologically in murine animal modelsMicroCures aims to optimize the efficacy of a novel treatmentnanoparticle encapsulated FLsiRNAFLNP sithrough a dose response assay to directly enhance the wound closure and healing function of corneal epithelial cells thereby addressingfor the first timethe challenge of accelerated healing and tissue repair in corneal woundsThuswound healing would reduce scarring and painimprove visionand lower the risk of infection due to faster wound closureas well as improve restoration of corneal architectureThe goal for this proposed project is to optimize the FLsiRNA concentration encapsulated in the nanoparticle via a dose response study in terms of efficacySpecific Aimand the best concentration used in a preliminary safety evaluationSpecific Aimin a rat animal model of corneal alkaline burnsin preparation for a larger and more comprehensive Phase II IND enabling studiesTime to wound healing and histopathology at the wound siteas well as local toxicity will be evaluatedAt the end of the project periodwe will show that FLNP si is both safe and efficacious for the treatment of corneal alkaline burn wounds Corneal injury is one of the most common causes for ocular related hospital visitsgiving rise to tissue scarring and corneal hazeas well as reducing visual acuityAt present there is no clinically proven treatment to improve corneal wound healing due to alkaline burnsOur goal is to develop and bring to the market a novel therapeutic that stimulates wound healing in the cornea via RNAimediated silencing of the microtubule regulatory proteinFidgetin LikeFL