The comorbidity spectrum of ID, autism, and schizophrenia affects more than 1% of the population and has been associated with a total cost of approximately 150 billion euros in Europe alone. These costs include direct health care and non‐medical costs (e.g., travel and home services), and indirect costs (e.g., lost productivity). In addition, affected individuals suffer from social problems and/or physical health problems, resulting in a reduced quality of life. Accurate diagnosis in a situation where many symptoms overlap and subsequently making the right connection to effective intervention are major limitations.
COSYN aimed to address the basis of ID, autism, and schizophrenia by studying the genes and pathways involved in this process and by identifying the interactions through which the disease phenotype develops in normal and in disease conditions, with an emphasis on synaptic function, as early steps of neuropsychiatric disorders are expected to impact synapse function.
COSYN used literature data and genomic data generated by partners (mainly genome sequence data, genome-wide association arrays, and copy number variant assessments). Using these data, we selected patients with both evidence of clinical comorbidity and possessing a rare genetic variant of strong effect. Gene dysfunction was modelled using patient-derived cellular models, and experimentally tested in order to provide assays for identifying targets amenable to therapeutic drug development. Some testing of genes and pathways involved using animal model systems (mouse) but mostly we used patient-derived neurons.
COSYN used human pluripotent stem cell lines, in particular human induced pluripotent cells (hiPSC) based on their capacity to self-renew and differentiate into virtually all cell types of the human body.
hiPSC were generated by reprogramming of somatic cells (e.g., white blood cells) from patients with rare mutations relevant to ID, autism, and schizophrenia as well as from healthy donors. From these approaches, COSYN generated cell models that enabled validation of drug targets, provided new diagnostic tools, nosological information, and new drug discovery programs that will (eventually) directly benefit patients suffering from these disorders.