Study of perisynaptic Schwann cells contribution on NMJ reinnervation efficiency in ALS

One of the earliest changes in ALS occurs at the neuromuscular junctions (NMJs), the points where nerves connect to muscles. These changes happen even before symptoms appear, making NMJs a potentially important target for new treatments. Under normal conditions, special cells called perisynaptic Schwann cells (PSCs) help maintain and repair NMJs. However, in ALS, PSCs do not work properly because of abnormal signaling, which prevents effective repair. As a result, NMJs become unstable and go through repeated cycles of losing and regaining nerve connections (denervation and reinnervation), that ultimately fail to maintain the neural pathway.

Simon will focus on trying to understand why NMJs fail to recover fully in ALS. They have developed a novel method to study this process by selectively damaging a few nerve fibers and then observing how NMJs recover over time. By collecting electrical activity and advanced imaging, they are able to compare repaired NMJs with healthy ones. Next in the project, Simon will also test whether restoring normal PSC function can improve NMJ recovery using a targeted gene therapy approach. By understanding this repair process, Simon’s research can help us identify new strategies to protect NMJs and develop better treatments for ALS.

Beyond research, Simon actively engages in ALS advocacy, fundraising, and science outreach, reinforcing his commitment to people affected by ALS. His journey began in neurology clinics in France, where he witnessed firsthand the reality of ALS. Motivated by the resiliency of our community and the urgency of the disease, Simon transitioned from clinical practice to research in Canada, determined to push our understanding of ALS and contribute to the field.

The ALS Canada Research Program has proudly supported novel work in the neuromuscular field since 2002. Simon’s supervisor, Dr. Richard Robitaille, a globally respected leader in the field, has been supported multiple times. Our awards provided seed funding for the work that culminated 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.