Automated Patch Clamp & iPSC: Cellular, molecular & electrophysiological characterization of CDKL5 deficiency disorder

Drug discovery in neuroscience faces many unique challenges, including access to the central nervous system through the blood-brain barrier and complex biology and circuitry that is still being defined. In order to overcome these challenges to identify treatments for neurodevelopmental disorders, scientists need better preclinical data. One requirement for improved preclinical data is a robust model system. Recent advances in stem cell technology have allowed for the creation of stem cells from patient skin or blood cells, called induced pluripotent stem cells (iPSCs). These patient-derived iPSCs can then be differentiated into neurons to model how a patient mutation causes changes in neuronal function compared with a healthy control neuron, followed by testing of therapeutics for the reversal of these in vitro phenotypes. This strategy has already successfully transitioned from the bench to the clinic for amyotrophic lateral sclerosis (ALS). We have recently used this technology to better understand the cellular and molecular consequences of loss of CDKL5 in iPSC-derived neurons. With Sophion’s automated patch technology, we can begin to understand the functional changes taking place in neurons with loss of CDKL5 function. Together, these model systems and technologies can be used to screen for and identify novel therapeutic targets for neurodevelopmental disorders. Our guest speaker, Dr Liz Buttermore from Boston Children’s Hospital, will talk about the challenges facing drug discovery in neuroscience