Project team leader
Autism Spectrum Disorders (ASD) are a heterogeneous group of neurodevelopmental disorders which complicates the identification of an effective therapeutic solution. More than 75 % of people suffering from Phelan McDermid Syndrome (PMS) exhibits ASD symptoms. This rare disease is due to a deletion/alteration in chromosome chromosome 22 (22q13) leading to a haploinsufficiency of SHANK3 expression. SHANK3 encodes a scaffolding protein in the postsynaptic density of excitatory synapses. A reduced expression of SHANK3 leads to an alteration in neuron morphology and synapse connectivity via unknown mechanism.
After the identification of a developmental hyperdifferentiation phenotype in patient-derived iPS cells during the first 6-14 days of differentiation into glutamatergic neurons, a fully automated process was developed allowing us to perform a >7000 molecules screening to reverse hyperdifferentiation. Validation of identified hit compounds was performed in a synaptic imaging assay after 28 days of differentiation. In summary, we performed phenotypic screening using specific pathological hallmarks of a neurodevelopmental disease in patient-derived of cells.