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Organ-Chip ALS Model Reveals Glutamate Signaling Alterations in Patient Motor Neurons

This fluidic organ-chip blends patient neurons with a blood-brain-like barrier to uncover early ALS progression.

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Overview

  • Researchers seeded iPSC-derived spinal motor neurons into top channels of a porous microchip above a lower chamber lined with blood-brain barrier cells to simulate circulation.
  • Transcriptomic and proteomic analyses identified ALS-specific dysregulation in neurofilament, glutamatergic and synaptic signaling pathways within patient motor neurons.
  • Motor neurons cultured under continuous fluid flow matured more completely than those in static dishes, enhancing model fidelity.
  • Spinal microtissue models from ALS patients secreted elevated inflammatory proteins and exhibited progressive motor neuron death, recreating key disease hallmarks.
  • High-throughput screening of 190 FDA-approved compounds in patient microtissues pinpointed a drug class that normalized inflammatory markers and improved neuron survival.