A therapeutic approach for rare genodermatoses caused by aberrant connexin hemichannels

Keratitis-Ichthyosis-Deafness (KID) syndrome is a rare genetic disease characterized, among other symptoms, by vascularising keratitis and hyperkeratotic skin lesions. This disease usually induces severe skin manifestations that sometimes can became letal. For KID syndrome there is still no cure. It is due to specific mutations in the gene of connexin 26, a membrane protein that form channel used by the cell to exchange ions and small molecules with the extracellular environment. Channels formed by mutated connexins are “leaky”, deregulated and hyperactive. We designed and produces an antibody, named abEC1.1, that identifies and binds connexin 26 with high affinity and specificity. We already proved that abEC1.1 is able to inhibit the mutated connexins channels hyperactivity (published paper). The main aim of this research project is to study the in vivo effects of the antibody in animal models to test the abEC1.1 feasibility as a KID syndrome cure. We planned to conduct this study on two different mouse strains, each expressing a different connexin 26 mutation. These animals express several symptoms of human pathology and therefore are considered a good experimental model to study KID syndrome. The abEC1.1 antibody will be administrated to the animals, at different disease stages, either topically (by means of a cream rubbed on skin) or systemically (by injection). The treatment efficacy will be assessed by measuring the antibody effects on skin lesions, on cutaneous layers organization and on stratum corneum thickness. The results of these experiments could path the way for clinical application of abEC1.1 on KID syndrome patients.