Target validation and drug discovery towards a therapy for the Rett Syndrome.

Rett syndrome (RTT) (OMIM 312750) is a progressive neurodevelopmental disorder that predominantly affects girls  and is caused by loss-of function mutations in the methyl-CpG-binding protein 2 (MeCP2). To date only symptomatic treatment is available. In this project we will validate on the one hand the direct interaction between the transcriptional co-activator lens epithelium-derived growth factor p75 (LEDGF/p75) and MeCP2 as a putative target for RTT treatment. In a second approach we will perform drug discovery to regain MeCP2 function in the most prevalent disease associated variant: T158M . This project will contribute to a better understanding of the pathogenesis of the disease and may lead to novel treatment strategies.