Novel therapeutic approaches for AEC syndrome

AEC (Ankyloblepharon- Ectodermal defects- Cleft lip/palate) syndrome is a rare genetic disease mainly characterized by severe skin lesions, defects in the hair, nails, sweat glands and teeth, closure of eyelids margins, and cleft lip and/or palate. Skin erosions appear at birth or soon after, are very severe and can last several years, resulting in recurrent infections. This disease is caused by genetic defects in p63, a crucial regulator of the skin. This project aims at testing two treatments for the skin lesions. For the first one we will use the CRISPR/CAS9 technology, the molecular scissors for which the Nobel prize has been awarded in 2020, to correct the DNA. In this case the correction is permanent but requires a biopsy, expansion in vitro of epidermal cells, genetic correction, and reimplantation on the wounds. The second treatment is with novel drugs that we recently identified in a large screening. The efficacy, toxicity and mode-of-action of these drugs will be tested in simple in vitro models, in a mouse model for the disease, and in human epidermal cells. The combination of studies in human cells derived from patients and in mouse model using different approaches will be instrumental to design novel therapies for this untreatable disease.