EEC-Clear: towards customized allele-specific CRISPR/Cas gene editing for the treatment of ocular surface disorder in EEC syndrome

EEC syndrome is a rare congenital disorder characterized by ectrodactyly ("claw-like hand") and anomalies of the palate and other tissues of ectodermal origin, such as nervous tissue, stratified epithelia, hair, and nails. The disease is dominantly inherited and, in over 90% of cases, is caused by mutations in the TP63 gene, encoding for p63. This protein is crucial for both development and maintenance of various epithelial tissues, including the epidermis and corneal surface. Most EEC patients suffer from corneal defects linked to the progressive depletion of limbal stem cells, responsible for regenerating the ocular surface, essential for corneal transparency and visual acuity. This project aims to develop a new therapeutic approach to address the progressive corneal opacification and loss of vision, which significantly impact the quality of life for EEC patients and represent their primary unmet medical need. We propose to use a gene editing approach to restore the correct function of p63 protein. The project leverages the research team's extensive expertise in cell therapy for ocular surface reconstruction (leading to the development of Holoclar, the first advanced therapy approved in Europe) and gene therapy (successfully applied as a life-saving treatment for "Butterfly Children" with Epidermolysis Bullosa). This combined experience is expected to accelerate the translation from bench to bedside.