When mice and humans experience partial damage to their spinal cords, they initially face paralysis followed by a remarkable spontaneous recovery of motor function. However, when a complete spinal cord injury occurs, this natural healing process doesn’t take place, leading to no recovery. To achieve meaningful recovery after severe injuries, strategies are needed to promote the regeneration of nerve fibers. Yet, the conditions necessary for these strategies to successfully restore motor function have remained elusive.
Mark Anderson, one of the senior authors of the study and the director of Central Nervous System Regeneration at .NeuroRestore, along with researchers from UCLA and Harvard Medical School, utilized advanced equipment at EPFL’s Campus Biotech facilities in Geneva to conduct detailed analyses. They aimed to identify the specific type of neuron involved in the natural repair of spinal cords following partial injuries.
Through single-cell nuclear RNA sequencing, the team not only unveiled the precise axons that must regenerate but also discovered that these axons must reconnect to their natural targets to fully restore motor function. These significant findings have been published in the journal Science.
Towards a combination of approaches
Their discovery has guided the development of a multifaceted gene therapy approach. The researchers activated growth programs within the identified neurons in mice, prompting the regeneration of their nerve fibers. They also increased specific proteins to support the growth of these neurons through the injury site and administered guidance molecules to attract the regenerating nerve fibers to their natural destinations below the injury.
“We drew inspiration from nature as we crafted a therapeutic strategy that mimics the spontaneous spinal cord repair mechanisms observed after partial injuries,” says Squair.
Remarkably, mice with complete spinal cord injuries regained the ability to walk, displaying walking patterns akin to those seen in mice that naturally resumed walking after partial injuries. This discovery unveiled a previously unknown requirement for regenerative therapies to successfully restore motor function following neurotrauma.
“We anticipate that our gene therapy will work synergistically with our other approaches, such as electrical spinal cord stimulation,” notes GrĂ©goire Courtine, a senior author of the study and co-leader of .NeuroRestore alongside Jocelyne Bloch.
“We believe that a comprehensive solution for treating spinal cord injuries will necessitate both strategies—gene therapy to regrow relevant nerve fibers and spinal stimulation to maximize the functional capacity of these fibers and the spinal cord below the injury.”
While there are still numerous hurdles to overcome before applying this gene therapy in humans, the researchers have taken the initial steps toward developing the necessary technology for future implementation.