Ahn LY, Coatti GC, Liu J, Gumus E, Schaffer AE, Miranda HC.
Journal of Neuroscience Research, 2020
In this paper, the authors report their investigation into the pathophysiological mechanism underlying the pathogenic variants in ACTL6B patients. These patients often present with early infantile epileptic encephalopathy, global development delay, cerebral atrophy, and abnormal CNS myelination. Using patient-derived neurons they were able to show reduced protein stability, and dysregulation of target gene expression important for neuronal disease and development. Furthermore, Axion's MEA system recorded elevated electrophysiological activity in the patient-derived neurons consistent with the patient phenotype.
How Axion's multielectrode array system was used:
To record the population-wide neuronal activity of the patient and unaffected controls, the iPSC-derived NPCs were placed in 48-well MEA plates. Neural differentiation was induced and MEA recordings were made every second day and analyzed with the AxIS software neural module. The measurement of neuronal activity was to correlate the clinical manifestations of seizures in patients. By recording the extracellular action potentials as a measurement of neural functionality (mean firing rate) and excitability (bursts). Spontaneous activity was observed on day 13 in both affected and unaffected cells. The patient-derived neurons had a increased mean firing rate, and increased burst activity. Together this is consistent with the seizure presentation in patients.