VEGFA as a potential therapeutic target to enhance motor recovery following acute and chronic nerve injury

2021 Pilot Project Read More

Investigators

Principal Investigator: Alison Snyder-Warwick (WashU Surgery)
Collaborators: Jianjun Guan ( WashU Mechanical Engineering & Materials Science)

Description

Injuries to the Peripheral Nervous System are burdensome on individuals and society as a whole. Despite advances in neuroscience and reconstructive nerve surgery, recovery after peripheral nerve injuries often remains incomplete. Functional outcome worsens with increased time for nerves to reconnect with muscles. Compared to nerves, less investigative focus has centered on the muscle and the neuromuscular junction (NMJ), which is the interface between nerve signals and muscle movements. Terminal Schwann cells (tSCs) help with NMJ function, and following nerve injury, these tSCs guide nerve fibers back to the NMJs. We have identified Vascular Endothelial-derived Growth Factor A (VEGFA) as a key growth factor required for NMJ recovery after nerve injury with immediate nerve repair. Specifically, we have found that blocking VEGFA signaling results in a reduction of tSCs guidance of nerve fibers to the NMJs and overall fewer nerve fibers reaching NMJs. Additionally, we showed an increase in VEGFA receptors on tSCs after injury. Clearly, VEGF signaling loss after early nerve repair results in worse muscle function. What happens to VEGFA and the NMJ after delayed repair is not known, nor is the possible benefit of VEGFA enhancement to muscle after nerve injury in either the acute or chronic settings. This project investigates whether exogenous VegfA delivery to the end target muscle following nerve injury and immediate or delayed repair can enhance functional recovery. If successful, additional studies will be planned to translate this finding clinically for localized delivery at the affected muscle. With this knowledge, treatment of the high number of nerve injuries can be improved.

Investigators

Pilot project teams include Hope Center faculty members and others. For more about Hope Center faculty on this team, click below.

Alison Snyder-Warwick