Worldwide, an estimated 3 million people live with a chronic spinal cord injury (SCI), and more than half do not recover the ability to stand or walk with current standards of care. Through an ERC Starting Grant, we had developed a new therapy based on electrical spinal cord stimulation that restored standing and walking in rodent models of SCI.
The objective of HOW2WALKAGAIN was to leverage the most advanced neurotechnologies to identify the neural mechanisms underlying the recovery of walking during electrical spinal cord stimulation. Our ultimate goal was to exploit this fundamental knowledge to translate this therapy in humans.
During this project, we found that electrical spinal cord stimulation modulates specific neuronal subpopulations in the spinal cord through the recruitment of afferent fibers innervating sensory receptors embedded into muscles, called proprioceptors. This understanding allowed us to develop more advanced stimulation protocols that exploit the anatomical organization of the proprioceptive system to mediate a more robust facilitation of leg movements. Translation of these protocols in clinical settings allowed nine individuals with chronic SCI to regain the ability to walk. Moreover, neurorehabilitation enabled many individuals to regain voluntary control over the activity of previously paralyzed muscles, even when the stimulation was turned off. This neurological recovery had not been observed with conventional stimulation protocols. Consequently, we modelled all the features observed in humans in rodent models in order to identify the mechanisms underlying this unexpected recovery. We thus deployed whole-nervous system imaging, single-cell technologies, and cell-specific interrogations in transgenic mice to catalogue the molecular choreography of recovery from spinal cord damage during neurorehabilitation supported by electrical spinal cord stimulation. We discovered that this therapy promotes the directed growth of neural projections from specific brain regions onto specific neuronal subpopulations in the spinal cord that become essential to walk after paralysis.
This understanding also allowed us to target other neurological functions that are impacted by SCI. For example, many individuals with severe SCI showed abnormally low levels of blood pressure, called orthostatic hypotension, that escalate risks of cardiovascular diseases and dramatically impact the quality of life. We found that we could use the same principles to modulate the sympathetic circuits that regulate blood pressure. This understanding supported the development of a spinal cord neuroprosthesis that precisely regulates blood pressure in real-time.
Our ERC proof-of-concept is enabling the translation of these scientific advances into tailored clinical devices for the recovery of mobility and hemodynamic stability. To accelerate this translation, we founded the start-up ONWARD Medical, which aims to bring this therapy to the market. Our ultimate goal is to bring these clinical innovations to the community of people with SCI.
