Vagus nerve stimulation demonstrates unprecedented recovery rates for spinal cord injuries

Vagus nerve stimulation demonstrates unprecedented recovery rates for spinal cord injuries

In a new clinical study, researchers at the Texas Biomedical Device Center (TXBDC) at the University of Texas at Dallas demonstrated unprecedented rates of recovery for spinal cord injuries.

In this study published in the prestigious journalNatureOn May 21, people with incomplete spinal cord injuries safely received a combination of stimulation of a nerve in the neck with progressive, individualized rehabilitation. This approach, called closed-loop vagus nerve stimulation (CLV), resulted in significant improvements in arm and hand function in these individuals.

The unprecedented results position UT-Dallas scientists to move forward with a pivotal trial — the final hurdle toward potential Food and Drug Administration (FDA) approval of vagus nerve stimulation to treat upper insult impairment due to spinal cord injury.

This approach is based on over a decade of neuroscience and bioengineering efforts by UT Dallas researchers. The therapy uses electrical impulses sent to the brain via a tiny device implanted in the neck and timed to occur during rehabilitation exercises. Previous work by UT Dallas researchers has shown that stimulating the vagus nerve during physical therapy rewires areas of the brain damaged by stroke and can lead to improved recovery.

Dr. Michael Kilgard, the Margaret Footede Jonsson Professor of Neuroscience in the School of Behavioral and Brain Sciences and the corresponding author, explained that the treatment of spinal cord injuries with CLV differs from conditions matched in previous studies.

In stroke, people doing therapy alone can get better and adding CLV multiplications can make this improvement. This study is different: therapy alone for spinal cord injuries did not help our participants at all. “

Dr. Michael Kilgard, the Margaret Founde Jonsson Professor of Neuroscience in the School of Behavioral and Brain Sciences

The study included 19 participants with chronic, incomplete cervical spinal cord injury. Each person completed 12 weeks of therapy and played simple video games to trigger specific upper limb movements. The implant activated upon successful movements, resulting in significant benefits to arm and hand strength.

"These activities allow patients to regain strength, speed, range of motion and hand function. They simplify daily life," said Dr. Robert Rennaker, professor of neuroscience and the Texas Instruments Distinguished Chair in Bioengineering, who designed the implanted CLV device using miniatures.

The study served as both a Phase 1 and Phase 2 clinical trial and included randomized placebo control in the first phase, in which nine of the 19 participants received sham stimulation rather than active treatment during the first 18 therapy sessions and then received CLV during the final 18 sessions.

Participants ranged in age from 21 to 65 years and were 1 to 45 years post-injury. Neither of these factors nor the severity of impairment in subjects with hand movement influenced the degree of response to treatment.

“This approach produces results regardless of these factors, which often cause significant differences in the success rates of other types of treatment,” said study co-author Dr. Jane Wigginton, physician and chief medical officer at TXBDC, co-director of UTD's Clinical and Translational Research Center, and Medical Science Research Director at the Center for Brainithealth.

“From a medical perspective, it's remarkable,” said Wigginton, who planned clinical interactions and patient protection for the study.

TXBDC has worked to treat a variety of diseases with CLV over 13 years of research. As a result, the FDA has approved vagus nerve stimulation to treat upper limb movement in stroke patients.

Wigginton said the latest findings are particularly exciting because they help people for whom there is no existing solution.

“The people in this study have now gained the ability to do things that are meaningful to them and impactful in their lives.”

The latest generation of the implantable CLV device designed by Rennaker is approximately 50 times smaller than its version three years ago. It does not prevent patients from receiving MRIs, CT scans, or ultrasounds.

A pivotal Phase 3 study includes 70 participants at multiple U.S. institutions specializing in spinal cord injuries.

Co-author Dr. Seth Hays, associate professor of bioengineering and colleague Eugene McDermott in the Erik Jonsson School of Engineering and Computer Science, led the CLV project, which dates back to its earliest studies.

“Prior to this study, no person with spinal cord injury had ever received CLV,” he said. "This is the first evidence that profits can be made. Now we will determine how to do this in the most effective way."

Hays cautioned that it is not a foregone conclusion that the therapy will be made available to patients after the next study.

"We still have a long way to go. For many reasons - financial, regulatory or scientific - this could still die on the vine," he said. “But we have positioned ourselves to be successful.”

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, the Baylor Scott & White Research Institute and the Baylor Scott & White Institute for Rehabilitation.

“This was the hardest-working, most altruistic group of professionals, and it was incredibly impactful,” Wigginton said.

Noting that even outpatient surgery is complex for people with mobility impairments, Rennaker added: "These patients said, 'Setting up the device in me - that's a big commitment. They deserve credit for paving the way for others.'

Other UTD-affiliated co-authors included Joseph Epperson BS’20, PhD’24, TXBDC Research Associate; Cognition and neuroscience doctoral student Emmanuel Adehunoluwa MS’23; Amy Porter Mba’20, TXBDC Director of Operations; Hollle Carey Gallaway Mba’23, TXBDC Research Biomedical Engineer; and David Pruitt Ms’14, PhD’16.

Kilgard has a financial interest in MicroTransponder Inc., which markets vagal nerve stimulation therapy for stroke. Rennaker is the founder and CEO of Xnerve, which developed the device used in this study.

The research was funded by a grant (N6001-17-2-4011) from the Defense Advanced Research Projects Agency (DARPA), an agency of the Department of Defense, and the Wings for Life Accelerated Translational Program.

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