Innovative 'ALS on a Chip' Model Uncovers Changes in Motor Neuron Signaling

Researchers at Cedars-Sinai have developed a groundbreaking laboratory model that mimics the complex features of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease. Utilizing stem cells derived from ALS patients, the team constructed a sophisticated 'organ-on-a-chip' that offers fresh insights into the disease's underlying mechanisms.

The process involved converting adult cells from ALS patients into stem cells, which were then differentiated into motor neurons—the cells responsible for muscle movement that degenerate in ALS. These motor neurons were seeded onto microengineered chips, with additional cells forming a blood-brain barrier in a connected channel, simulating blood flow and nutrient exchange. A parallel set of chips with healthy cells served as controls.

Using advanced genetic analysis, over 10,000 genes were examined in both groups, revealing that early-stage motor neurons from ALS patients showed subtle yet significant differences compared to healthy cells. Notably, the study uncovered altered glutamate signaling, a neurotransmitter involved in neural communication. Excessive glutamate release has long been suspected to contribute to motor neuron death in ALS, and these findings support that hypothesis.

This dynamic chip model, which incorporates fluid flow to mimic blood circulation, allowed motor neurons to mature more fully than traditional static cultures. This enhanced development enabled researchers to detect differences that previous studies might have missed, emphasizing the importance of a realistic environment for studying neurodegenerative diseases.

Dr. Clive Svendsen explained that while early studies did not show many differences, the realistic conditions of the microfluidic chips revealed crucial alterations in neural signaling pathways. The team now plans to investigate whether the observed increased glutamate activity directly causes neuronal damage or death and to explore potential therapeutic interventions by testing drugs on the blood vessel component of the models.

This innovative approach provides a promising platform for understanding the initial stages of ALS and testing potential treatments, bringing researchers a step closer to deciphering the complex puzzle of this deadly disease.