When it comes to spinal cord injuries, both mice and humans share a common pattern of initial paralysis followed by some degree of spontaneous recovery of motor function when the damage is partial. However, when the spinal cord injury is complete, this natural repair mechanism fails, leaving patients with no chance of meaningful recovery.
Overcoming the challenges posed by severe spinal cord injuries requires strategies that promote the regeneration of nerve fibers, but finding the right conditions for these strategies to successfully restore motor function has remained a complex puzzle. Five years ago, a groundbreaking discovery marked a significant step in the field of spinal cord regeneration.
Scientists demonstrated that it was possible to regenerate nerve fibres across anatomically complete spinal cord injuries. However, they soon realized that this regeneration alone was insufficient to restore motor function. The newly regenerated nerve fibres were failing to connect to the appropriate targets on the other side of the injury. This realization led to the understanding that a more comprehensive approach was needed to address the complex issue of spinal cord injuries.
Mark Anderson, a senior author of the study and the director of Central Nervous System Regeneration at. Neurorestorative, as well as a scientist at the Wyss Centre for Bio and Neuro engineering, was among those pioneering this research effort. Collaborating with colleagues from UCLA and Harvard Medical School, the scientists embarked on an ambitious journey to unravel the intricacies of natural spinal cord repair following partial spinal cord injuries. To achieve this, they utilized cutting-edge equipment and facilities at EPFL’s Campus Biotech in Geneva.
Their approach involved conducting in-depth analyses to identify the specific type of neuron responsible for the natural repair of spinal cords after partial injuries. The breakthrough came when they employed single-cell nuclear RNA sequencing, a sophisticated technique that not only pinpointed the specific axons needing regeneration but also highlighted the crucial requirement for these regenerated axons to reconnect with their natural targets for the restoration of motor function. The results of their research were published in the prestigious journal Science.
Building upon this newfound knowledge, the scientists devised a multifaceted gene therapy approach. This innovative strategy aimed to activate growth programs within the identified neurons in mice to stimulate the regeneration of their nerve fibres. Additionally, the scientists upregulated specific proteins to facilitate the growth of these neurons through the lesion core, the damaged region of the spinal cord. To ensure that the regenerated nerve fibres found their way to their intended destinations below the injury, the researchers administered guidance molecules.
The inspiration for this comprehensive therapeutic strategy was drawn from nature itself. The goal was to replicate the spinal cord repair mechanisms that naturally occur after partial injuries and apply them to cases of complete spinal cord injury.
In a remarkable turn of events, mice that had suffered anatomically complete spinal cord injuries exhibited an astonishing recovery of their ability to walk. Their gait patterns closely resembled those observed in mice that had naturally resumed walking after partial injuries. This remarkable observation unveiled a previously undiscovered condition necessary for regenerative therapies to successfully restore motor function after neurotrauma.
The scientists believe that their gene therapy approach holds immense promise. They anticipate that it will complement their other procedures, such as electrical stimulation of the spinal cord, which are designed to maximize the capabilities of both the regenerated nerve fibres and the spinal cord below the injury in generating movement.
However, while this groundbreaking gene therapy represents a significant leap forward in spinal cord injury treatment, there are still numerous hurdles to overcome before it can be applied to human patients. Despite these challenges, the scientists have taken the initial steps toward developing the necessary technology to make this transformative approach a reality in the years to come. The quest to unlock the secrets of spinal cord regeneration has yielded a remarkable breakthrough.
By understanding the specific neurons and conditions required for successful regeneration, scientists have devised a gene therapy approach that has the potential to restore motor function in cases of complete spinal cord injuries. While there is still work to be done, this research offers newfound hope to individuals who have longed for a solution to the devastating consequences of spinal cord trauma.