NF‐κB activation in astrocytes drives a stage‐specific beneficial neuroimmunological response in ALS

The paradox of neuroimmune activation in ALS

23 October 2018

Star-shaped support cells in the brain activate an immune response that helps protect against motor neuron loss in the early stages of amyotrophic lateral sclerosis (ALS). Yet, this same immune activation can accelerate neurodegeneration in later stages of the disease.

Findings from a mouse study, that included scientists from Roche, suggest that stage-dependent modulation of this immune process may be an effective therapeutic strategy for ALS patients.

The researchers activated a key cell-signaling pathway in the spinal cord astrocytes of a mouse model of ALS. They observed a proliferation of neuroimmune cells, called microglia, which resulted in delayed symptom onset but accelerated disease progression.

Pre-symptomatic treatment with an experimental Roche drug designed to enhance microglia function by blunting the immunosuppressive function of cannabinoid CB2 receptors led to a decrease in disease burden on a molecular level. A similar strategy could prove beneficial for those with a genetic risk for ALS who have yet to exhibit signs of the disease.

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References

1. The EMBO Journal 37, e98697 (2018). doi: 10.15252/embj.201798697