Characterization of a new therapeutic strategy for Phelan McDermid syndrome by rescuing dysregulated protein synthesis

Loss of a copy of the SHANK3 gene is the cause of Phelan-McDermid syndrome (PMS), a rare neurodevelopmental disorder. The biological basis of PMS is still unclear and, at the moment, there are no approved treatments that tackle the symptomatology of these patients. Protein synthesis is essential for neuronal functions and alteration in protein synthesis have been found in different neurodevelopmental disorder. Our preliminary results obtained studying mice and human neurons derived from PMS patients stem cells suggest that absence of Shank3 leads to a reduction in protein synthesis in neurons that might be the cause of some behavioral abnormalities displayed by PMS patients. In this project we aim to clarify at the molecular level how Shank3 affect protein synthesis. The results of our study will allow to identify new possible molecular target to develop new treatments for PMS patients