Dissecting the Aristaless-related Homeobox Epilepsy path to find druggable target molecules

Intellectual Disability (ID) with seizure is a group of incurable brain diseases with great impact on human health and society. The Aristaless-related homeobox gene (ARX) is one of the most frequently mutated genes in a spectrum of X-chromosome diseases with Epilepsy as their cardinal feature. To date, there is no cure for the symptoms associated to ARX-PolyAlanine mutations. Unfortunately, seizure associated to these mutations is severe, occurs very early in the post-natal life and is resistant to all standard epileptic drugs; this has a dramatic impact on the development and on the quality of life of these children. In this project we want to test an alternative treatment for this symptom and improve our understanding of the genetic and pathological aspects of ARX-PolyAlanine mutations. We have identified two genes which are targets of ARX and whose mutations lead to syndromes very similar to those induced by ARX mutation. We believe that by rescuing the activity of ARX defects with pharmacological agents we can prevent or treat the symptoms associated to ARX mutation. Therefore, we wish to test an epi-drug targeting ARX-defects to rescue Epilepsy and abnormal behaviour in mouse models of PolyAlanine. All these novel findings will improve biomedical research in mental retardation and Epilepsy.