Signaling Process Gone Awry Could Explain ALS Progression

Researchers from the University of Copenhagen have gained new insights about ALS, by investigating the early development of the disease in a mouse model. The team found that inhibitory interneurons lose connection to motor neurons, and could explain why the motor neurons end up dying in ALS. Their findings were published in Nature Communications. 

"It is only natural that motor neurons have received major attention. They control our muscles, which is the challenge for ALS patients. Here, we wanted to investigate the circuit of interneurons in the spinal cord because they determine the activity of motor neurons. Since we found that there is a loss of connections between inhibitory interneurons and motor neurons that happens before the motor neuron death, we think that this loss could be a possible explanation for why the motor neurons ends up dying in ALS patients,” says Ole Kiehn, senior, co-corresponding author. 

Studying mouse models, the team showed that the loss of connection happens to fast motor neurons initially, and then moves on to V1 inhibitors.  "The V1 interneuron connectivity loss is paralleled by the development of a specific locomotor deficit in the pre-symptomatic phase with lower speed and changes in limb coordination in the ALS mice that is dependent on V1 interneuron connections to motor neuron,” Kiehn says.

The researchers underline that the mechanisms should be investigated in human patients as well. However, they do not have any reason to believe that the same or similar biological mechanisms are not at play in humans. Given the new understanding of the disease, the team hopes further research into the signaling process could reveal how to repair the nerve cell connection loss in ALS.