Tissue scarring associated with poor wound healing can be a serious problem, particularly when the scarring is in the eye. The exposed cornea is first to become involved in ocular infection, chemical or blast injuries. Worldwide, corneal diseases primarily resulting from infection, trauma, and surgical complications are responsible for 6 to 9 million cases of blindness in human patients. Poor corneal wound healing can result in permanent loss of corneal transparency and vision loss. Currently, there are limited medical and surgical treatments available to address this problem. Kalyra Pharmaceuticals has developed a series of novel potent, anti-scarring (anti-fibrotic) compounds, utilizing our toolbox of proprietay bioisosteres. With lead candidates in hand, we aim to demonstrate that these molecules can reduce scarring of the cornea after injury, via the Phase I proof of concept studies outlined below: Phase I: Demonstrate Reduction of Scarring in a Model of Corneal Wound Healing Aim 1. Preliminary formulation development for topical delivery to the eye Aim 2. Determine the extent of drug uptake in the cornea after topical administration Aim 3. Demonstrate efficacy by reducing scarring in a model of corneal wound healing Goal: Proof of concept for significant reduction of scarring of the cornea, and characterization of drug uptake in the cornea after topical administration. After the successful completion of the studies described in this Phase I application, we will continue the non- clinical development of a new treatment for reduction of fibrosis and scarring in the eye in Phase II.
Public Health Relevance Statement: Public Health Relevance: This project is focused on demonstrating proof of concept, for a new treatment to reduce scarring. Poor corneal wound healing and scarring in the eye can result in permanent loss of corneal transparency, and there are limited medical treatments available to address this problem. The purpose of this proposal is to develop a novel treatment to improve the healing of corneal wounds and reduce the extent of corneal scarring. Such a new therapy may profoundly alter how we treat corneal wounds in people in the future. A new treatment that reduces scarring can also be applied to other indications where improved wound healing is required.
NIH Spending Category: Eye Disease and Disorders of Vision; Injury (total) Accidents/Adverse Effects
Project Terms: Accounting; Address; Applications Grants; Architecture; Attention; base; Biological; Blast Injuries; Blindness; Chemical Injury; Cicatrix; Clinical; Collagen; Cornea; Corneal Diseases; Corneal Injury; corneal scar; Data; Development; Dose; drug discovery; Drug Kinetics; Effectiveness; Elements; Equilibrium; Evaluation; experience; Extravasation; Eye; Eye Infections; Eye Injuries; Facial Injuries; Fibroblasts; Fibrosis; Formulation; Future; Goals; Hand; Healed; healing; Hemorrhage; Homeostasis; Human; improved; Infection; Injury; Ischemia; Kidney; Lead; Liver; Lung; Mechanics; Medical; Modeling; Molecular Weight; Myofibroblast; novel; novel therapeutics; Operative Surgical Procedures; Oryctolagus cuniculus; Outcome; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacologic Substance; Phase; Process; Production; public health relevance; Publishing; research and development; response; Role; Sampling; Series; Skin; Soldier; Solubility; Surgical complication; Testing; therapy development; Time; Tissues; Topical application; Trauma; uptake; vascular inflammation; Vision; Visual; vzg-1 Receptor; Work; Wound Healing
