Functional study on a new pharmacological approach in the Rett Syndrome

Rett syndrome (RTT) is a neurodevelopmental disorder affecting predominantly 1: 10,000-15,000 females worldwide, caused by loss-of-function mutations in the Methyl-CpG-binding Protein-2 (Mecp2) gene. After an apparently normal development until 6–18 months of age, girls experience a rapid regression resulting in loss of acquired skills, profound intellectual disability, stereotypical movements, autistic features. Sensory and motor deficits are considered among the most debilitating symptoms in RTT patients, together with breathing alterations and seizure. In this study we intend to collect solid pharmacological results in an experimental model of Rett's pathology. The drug under investigation is known as a selective inhibitor of the ATM protein, a kinase that we have recently shown to regulate one of the main processes of neurodevelopment. In the laboratory we have already identified the mechanism by which this small molecule acts in MeCP2 deleted neurons. Now, in order to provide a new pharmacological approach in Rett syndrome, it is necessary to validate our positive data collected in vitro in more complex models that recapitulate the typical Rett symptomatology. Therefore, the project we propose fully satisfies the Telethon Mission, aimed at advancing biomedical research in genetic diseases by helping it move towards clinical application; in fact, our data may help develop a new therapy in Rett syndrome.