Untangle the endocannabinoid system alteration in ALS: a new therapeutic approach at the neuromuscular junction

Motor neurons are specialized cells in the brain that are responsible for controlling voluntary muscles. In ALS, these neurons break down and die, eventually leading to weakness and then paralysis of muscles. Besides motor neuron degeneration, an early sign of ALS is the loss of the neuromuscular junction (NMJ), the connection point between muscles and motor neurons. In the disease, the neuron terminals at the junction begins to retract, a process called denervation, leading to a disconnection between the brain and muscles.

Findings from Dr. Piovesana highlight that a specific receptor called endocannabinoid CB1 receptor (CB1R) plays an important role in the repair and maintenance of NMJ connections. The endocannabinoid system is a network of receptors and chemicals in the body that help regulate functions like sleep, appetite, and pain etc., and works to keep the body balanced. In ALS models in the lab, a loss of CB1R and an increase in certain enzymes that break down endocannabinoids seem to contribute to disease.

In this project, Dr. Piovesana will test whether restoring the function of this system can delay or prevent the disease from progression, ultimately improving motor function and survival. Additionally, she will look at blood and muscle samples to identify new biomarkers for ALS, which could help in diagnosing and monitoring the disease.

If successful, this study could aid the development of a new therapeutic approach for ALS. With the support of this award, Dr. Piovesana’s ultimate goal is to become a leading ALS researcher, achieving an independent lab, and producing key findings toward a world free of ALS.

The ALS Canada Research Program has proudly supported novel work in the neuromuscular field since 2002. Dr. Piovesana’s supervisor, Dr. Richard Robitaille, a globally respected leader in the field, has been supported multiple times. Our awards provided seed funding to what would culminate in an exciting clinical trial in 2024. Dr. Robitaille discussed the neuromuscular junction and his trial investigating a compound called darifenacin in an episode of our ALS Clinical Trial Unboxed series.