Authors: Elizabeth D. Buttermore, Gayathri Rajaram Srinivasan, Hellen Jumo, Amanda C. Swanson, Benjamin O’Kelly, Nina R. Makhortova, Mustafa Sahin, and Stelios T. Tzannis
Frontiers in Neuroscience, 27 July 2025
Scientists use the noninvasive Maestro MEA platform to measure the neural activity of iPSC-derived neurons from people with tuberous sclerosis, showing that mTORC1-selective inhibitors reduced hyperexcitability in a dose-dependent manner.
The mTOR pathway is a critical regulator of cell growth and function, and its dysregulation contributes to neurological disorders such as Tuberous Sclerosis Complex (TSC). In this study, researchers used the Maestro MEA platform to evaluate iPSC-derived TSC2-deficient neurons after treatment with rapamycin and several mTORC1-selective inhibitors. All three selective compounds reduced firing rate and synchrony in a dose-dependent manner, closely mirroring the effects of rapamycin. These findings suggest that mTORC1-specific inhibitors may provide therapeutic benefit for reducing neuronal hyperexcitability in TSC and related mTORopathies, with the potential for fewer side effects than current treatments.
