Restoration of proteostasis to address co-occurring conditions in Down Syndrome

This proposal addresses three co-occurring conditions in Down syndrome: cognitive performance, sleep disturbances and metabolic dysfunction. We hypothesize that excess gene expression due to an extra copy of chromosome 21 imposes protein folding stress and renders patients susceptible to any condition that exacerbates it, including the conditions listed above. Thus, we will test the therapeutic potential of phenyl- butyrate, an FDA-approved chemical chaperone that can relieve protein folding stress.