Prof. Dr. Edna Grünblatt
Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital
University of Zürich
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental and psychiatric disorders in children and adolescents often to persist into adulthood. The causes and pathophysiology of ADHD are still unknown; nevertheless, evidences point to implication of genetic and environmental factors that probably affect brain maturation and development. To date, none of the existing models for ADHD (in vivo or in vitro) fully mimic the entire phenotypic spectrum or genetic background of the disorder, which is needed for elucidating the molecular pathomechanism or therapy response. Therefore, there is a great need to establish a model that mirrors the developmental alterations of ADHD. Reprogramming human somatic cells into induced pluripotent stem cells (hiPSC) and differentiating them into a neuronal lineage is a new, powerful technology that provides live human neurons for modelling complex genetic conditions, such as neurodevelopmental disorders (e.g., ADHD). The primary aim of the project is to establish a new, versatile, and de novo cell-based model for ADHD using hiPSC originating from the hair follicles (keratinocytes) of paediatric ADHD patients and controls. This unique cellular model will enable unprecedented investigation into the causative events of ADHD and the identification of specific biomarkers. Furthermore, this technology will allow therapeutics to be tested in cell types of interest, in a way that reflects response and effects reliably. Using this unique, patient-specific model we will try to find and characterize genetic alterations (mRNA, DNA polymorphism, epigenetic), possible altered neuronal pathways and changes in proteomics and broaden the understanding of ADHD’s causes.
Read more in:
Frontiers in Cellular Neuroscience "Improved generation of induced pluripotent stem cells from hair derived keratinocytes - a tool to study neurodevelopmental disorders as ADHD"
Leading Opinions "From hair follicles to neurons using induced pluripotent stem cells"