Final Report Summary - WALK AGAIN (Multi-pronged Strategies to Regain Voluntary Motor Functions after Spinal Cord Injury)
Severe SCI leads to a range of disabilities, including permanent motor impairments that seriously diminish the patients’ quality of life. In the framework of the ERC Starting Grant, my team and I developed a multi-pronged treatment that restored supraspinal control of leg movement after paralysis in rats. This treatment combines a serotoninergic replacement therapy and electrical spinal cord stimulation paradigms that immediately enable highly functional states of the spinal circuits that control the hindlimbs, located below the injury. To refine this electrochemical neuroprosthesis, we fabricated a spinal implant that combines multiple electrodes and a chemotrode. In parallel, we designed a control platform that titrates neuromodulation parameters in real-time based on movement feedback. Using these hardware and software, we conceived algorithms that precisely modulate leg movements, allowing paralyzed rats to execute complex, yet involuntary, walking behaviors. To restore voluntary movement, we developed a cutting-edge robotic system that encourages the rats to deliver voluntary descending drives in the presence of electrochemical stimulation. In the long term, this will-powered training regimen resulted in a pronounced remodeling of residual neural connection. Rats with a SCI leading to permanent paralysis regained supraspinal control over locomotion, but only during electrochemical stimulation. This intervention, termed neuroprosthetic rehabilitation, offers a novel window of opportunity to improve the quality of life for spinal cord injured individuals—a potential that has been confirmed during the first evaluations in primate model of spinal cord injuries and in paraplegic patients.