A groundbreaking clinical study published in Nature has demonstrated remarkable improvements in upper limb function for individuals with spinal cord injuries using a novel therapeutic approach that combines nerve stimulation with targeted rehabilitation.
Researchers from the Texas Biomedical Device Center (TxBDC) at The University of Texas at Dallas showed that closed-loop vagus nerve stimulation (CLV) produced meaningful recovery in arm and hand function for patients with chronic, incomplete cervical spinal cord injuries – a population that typically sees minimal improvement from rehabilitation alone.
"In stroke, people who do only therapy may get better, and adding CLV multiplies that improvement," explained Dr. Michael Kilgard, the Margaret Fonde Jonsson Professor of neuroscience and corresponding author of the study. "This study is different: Therapy alone for spinal cord injury didn't help our participants at all. It is truly groundbreaking that we're creating a gain where there otherwise would be none."
Study Design and Implementation
The trial enrolled 19 participants with chronic, incomplete cervical spinal cord injuries ranging from 1 to 45 years post-injury. Each participant received a miniaturized vagus nerve stimulation device implanted in the neck, which delivered precisely timed electrical pulses to the brain during rehabilitative exercises.
Participants were randomized into two groups: one receiving active CLV throughout 36 therapy sessions, and another receiving sham stimulation for the first 18 sessions followed by active CLV for the remaining 18 sessions. This double-blinded approach allowed researchers to directly measure the impact of the stimulation.
The rehabilitation regimen was personalized for each participant based on their abilities and included conventional exercises, computer-based rehabilitation, and functional tasks such as jar opening, writing, and key manipulation. Each participant completed approximately three 90-minute sessions per week.
Significant Clinical Improvements
The results were remarkable. Participants showed significant improvements in arm and hand strength, with many regaining abilities that enhance their independence in daily activities. Notably, these improvements occurred regardless of age, time since injury, or initial impairment severity – factors that typically influence recovery outcomes in other treatments.
"This approach produces results regardless of these factors, which often cause significant differences in success rates of other types of treatment," said study co-author Dr. Jane Wigginton, chief medical officer at TxBDC and co-director of UTD's Clinical and Translational Research Center.
The study served as both Phase 1 and Phase 2 clinical trials, with the results positioning the researchers to proceed with a pivotal Phase 3 trial – the final step before potential FDA approval. The upcoming trial will include 70 participants across multiple U.S. institutions specializing in spinal cord injury.
Technological Innovation
A key component of the study's success was the miniaturized CLV device designed by Dr. Robert Rennaker, professor of neuroscience and the Texas Instruments Distinguished Chair in Bioengineering. The current generation of the implantable device is approximately 50 times smaller than the version from three years ago and does not interfere with MRIs, CT scans, or ultrasounds.
The device works by delivering electrical stimulation to the vagus nerve in the neck precisely when patients successfully complete targeted movements during therapy. This stimulation is believed to enhance neuroplasticity – the brain's ability to reorganize neural pathways – which facilitates recovery.
"The concurrent timing of VNS and movement is based on the principle that precisely timed neuromodulatory feedback can direct specific synaptic changes to enhance recovery," the researchers explained in their Nature publication. This approach leverages the "synaptic eligibility trace," a phenomenon in which neuromodulatory reinforcement promotes plasticity in recently active neural networks.
Patient Impact and Future Directions
For participants in the study, the improvements translated to meaningful gains in daily functioning and independence.
"I can't overemphasize how satisfying it is as a physician to give hope and help to these spinal cord injury patients, who would come in with all kinds of complications and hopelessness," Dr. Wigginton said. "The people in this study have now gained the ability to do things that are meaningful for them and impactful in their lives."
Dr. Seth Hays, associate professor of bioengineering and co-author of the study, noted that while these results are promising, the path to widespread clinical availability still faces challenges.
"We still have a long road ahead. For many reasons — financial, regulatory or scientific — this could still die on the vine," he said. "But we have positioned ourselves to succeed."
The FDA has already approved vagus nerve stimulation for treating impaired upper-limb movement in stroke patients based on previous work by the TxBDC team. This latest advancement could potentially extend this therapeutic approach to the approximately 17,000 new spinal cord injury cases that occur annually in the United States.
The research team emphasized the importance of the dozens of people involved in the work – both the patients and TxBDC's partners at Baylor University Medical Center, Baylor Scott & White Research Institute, and Baylor Scott & White Institute for Rehabilitation.
"These patients said, 'Put that device in me' — that's a huge commitment. They deserve credit for paving the path for others," Rennaker acknowledged, highlighting the courage of the trial participants who underwent surgery and committed to the intensive rehabilitation program.
As the research progresses to the pivotal trial phase, the scientific community will be watching closely to see if this innovative approach can deliver a much-needed therapeutic option for individuals living with the long-term effects of spinal cord injury.
