Principal Investigator: Sameer B. Shah, PhD
Performing Organization: University of California, San Diego
Vehicular trauma and blast injuries are common causes of damage to the extremities of military personnel, often resulting in severe injury to peripheral nerves. Nerve injury results in motor impairment, sensory loss, and pain; beyond sensorimotor deficits, individuals experience feelings of frustration and helplessness. Functional recovery is often incomplete, and clinical outcomes are especially poor for severe nerve injuries. In partnership with Neuretix, Inc., to meet this challenge, our team has developed an innovative strategy to treat severe nerve injuries.
The best-case surgical outcomes for nerve injury occur following an end-to-end repair, in which severed stumps are directly reconnected, free of intervening grafts and conduits. However, this requires stumps to be in close proximity, which is uncommon. Thus, most large gaps are treated with a variety of grafts. Though autologous grafts are still considered “gold-standard,” outcomes remain poor, especially for large nerve gaps.
We have developed a graft-free biomedical device to repair large gaps. Strong preliminary data in rat and rabbit models demonstrated that our strategy restores neuromuscular function to levels beyond those enabled by autologous grafts. By applying modest levels of tension to the proximal nerve stump over a few weeks, thereby enhancing nerve growth in a manner analogous to nerve growth concurrent to limb lengthening, our technology bridges large nerve gaps and enables subsequent end-to-end repair (and its associated superior outcomes). In addition, this graft-free approach avoids adverse consequences currently associated with autografts.
We propose a series of scientific and regulatory objectives that will set the stage for first-in-human deployment. In particular, having demonstrated proof of concept in smaller animals, our next objectives are to adapt key components of our device to improve the functionality and safety profile of the NeuroLen, perform ex vivo and in vivo testing to confirm safety and efficacy in regulatory-supporting studies, and scale the device for human use.
Cumulatively, these enabling studies are expected to facilitate successful submission and regulatory approval of an IDE application to the USFDA, and associated IRB submission for a Phase 0/1 clinical trial. As a parallel objective, we will also perform experiments to demonstrate the efficacy of our device in nerve injury models in larger animals, providing insights for optimizing nerve lengthening as a regenerative strategy in more clinically-relevant model, to drive future technology development.
In conclusion, our project aims to deliver an innovative, safe, and clinically viable solution to address the unsolved challenge of peripheral nerve injury. The work completed under this award are the final de-risking steps required for first-in-human clinical deployment and eventual introduction of our technology to market.