Generation and functional characterization of patient-derived iPSCs for understanding the pathogenic mechanisms underlying altered neuronal function associated with CAMK2b gene mutations

The project will generate a human "model of study" for neuro-developmental syndrome due to CAMK2b gene mutation with the aim to unveil its pathogenic mechanisms and produce a knowledge able to lead to new hypotheses for the advancement of efficacious targeted therapeutic approaches. The model of study proposed in this project consists in generating induced pluripotent stem cells (named iPSCs), from patients’ skin biopsies, and in differentiating them into neurons with the same genetic background of the patients to study their morphological and functional characteristics during and following neuronal differentiation. The generated model will be patient-specific and it will help to elucidate the mechanisms leading to the observed clinical phenotypic variability. The data obtained will shed light on the altered phenotype of patient-derived neurons and this would be the first step toward the understanding of the mechanisms responsible for the disease and toward the generation of hypotheses to rescue the altered phenotype and to consider testing of different therapeutic approaches. In addition to this, the model and the phenotype characterization of the patient-derived neurons are necessary to test the efficacy of pharmacological treatments in rescuing the altered neuronal phenotype, and to perform patient-specific toxicity assay.