Disease models

A human cell-based model of Angelman syndrome could be used to screen therapies and identify therapeutic targets. Induced pluripotent stem (iPS) cell-derived neurons from two patients harboring deletions of the maternal chromosomal region containing ubiquitin protein ligase E3A (UBE3A; E6AP) and one patient with a loss-of-function mutation in maternal UBE3A recapitulated the defects in synaptic signaling and plasticity seen in Angelman syndrome patients, including low frequency of synaptic events, low percentage of synaptically active cells and low long-term synaptic potentiation. In the patient-derived neurons, topotecan -- which promotes expression of paternal UBE3A -- increased synaptic frequency compared with vehicle. Next steps include using the models to screen therapies and identify disease mechanisms and therapeutic targets...