Target validation and drug discovery towards a treatment for 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, I will validate on the one hand the direct interaction between the transcriptional coactivator lens epithelium-derived growth factor p75 (LEDGF/p75) and MeCP2 as a putative target for RTT treatment. In a second approach, I 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.