Breakthrough deep brain stimulation therapy restores walking after spinal cord injury

A spinal cord injury (SCI) disrupts communication between the brain and spinal cord, leading to partial or complete paralysis. But recent breakthroughs suggest an unexpected brain region could play a critical role in restoring mobility.

By targeting the lateral hypothalamus (LH) with deep brain stimulation (DBS), researchers have demonstrated significant recovery in walking ability for individuals with partial SCI. This novel approach, backed by detailed neurological mapping and clinical trials, promises to transform treatment for paralysis.

Scientists at EPFL and Lausanne University Hospital (CHUV), under the leadership of Grégoire Courtine and Jocelyne Bloch, developed a space-time brain atlas that maps active neurons involved in walking recovery. To their surprise, this atlas highlighted the LH—a region traditionally associated with functions like arousal and feeding, not locomotion.

Their work revealed that glutamatergic neurons in the LH (LHVglut2) are crucial for regaining walking ability after incomplete SCI. Activating these neurons reorganized spinal cord projections, enhancing motor recovery.

The team translated these findings into a pioneering DBS therapy targeting the LH. The results were striking. In animal models, DBS immediately improved walking, and over time, it fostered long-lasting recovery by strengthening residual neural pathways.

Encouraged by these preclinical outcomes, the researchers conducted a pilot clinical trial involving two participants with incomplete SCI. Both showed immediate and sustained improvements in mobility, even after the stimulation was turned off.

Wolfgang Jäger, a 54-year-old participant, described his transformation following the treatment. Injured in a 2006 skiing accident, he had been confined to a wheelchair for years. After receiving DBS, Jäger regained the ability to take steps, a freedom he had long missed.

"Last year on vacation, I walked down and back to the sea using the stimulation," he shared. Beyond walking, his independence in daily tasks improved significantly. "I can now reach things in my kitchen cupboards," Jäger added, highlighting the therapy's profound impact on quality of life.

The DBS procedure involves implanting electrodes into specific brain regions to modulate neural activity. While DBS has been used for decades to treat disorders like Parkinson's disease and essential tremor, applying it to restore walking is unprecedented. By targeting the LH, the team tapped into a previously unrecognized neural pathway critical for locomotor recovery.

The discovery of the LH's role in walking recovery marks a milestone in neuroscience. Through detailed brain-wide mapping, researchers identified the LH as a key player in mobilizing spinal cord-projecting neurons. These findings challenge traditional views on motor control and underscore the brain's capacity for adaptation.

“This research demonstrates the brain's central role in recovery from paralysis," said Courtine, a professor of neuroscience at EPFL and co-director of the .NeuroRestore center. "We discovered how to engage residual connections and augment recovery in people with spinal cord injury."

The breakthrough was made possible by advanced imaging tools at the Wyss Center, which provided high-resolution maps of neuronal activity. These tools allowed the team to pinpoint the LH's involvement in walking, a previously overlooked function of this brain region.

The study’s findings go beyond immediate mobility improvements. The therapy reorganized residual neural pathways, enabling durable recovery. This suggests DBS does more than stimulate movement—it may catalyze long-term changes in brain and spinal cord networks.

Future research aims to combine DBS with spinal implants that have already shown promise in restoring movement after SCI. “Integrating our brain and spinal stimulation approaches could offer a comprehensive recovery strategy,” said Courtine. Such combined therapies could enhance motor recovery and offer new hope for patients with SCI.

The success of DBS therapy hinged on surgical precision and patient feedback. Using advanced brain imaging, Bloch, a neurosurgeon at CHUV and co-director of .NeuroRestore, guided the electrode implantation process. Patients remained awake during the surgery, providing real-time feedback.

“When the electrode was in place, the first patient immediately said, ‘I feel my legs,’” Bloch recounted. “As we increased the stimulation, she said, ‘I feel the urge to walk!’ It was a breakthrough moment.”

This feedback validated the team's novel approach and underscored the LH's critical role in walking recovery. Bloch emphasized the importance of these discoveries for understanding brain functions and advancing neurosurgical techniques.

While the results are promising, further studies are necessary to establish the safety and efficacy of DBS targeting the LH. Researchers are investigating potential effects on body weight, hormonal profiles, psychological health, and autonomic functions.

As clinical trials expand, the focus will shift to optimizing protocols and exploring broader applications for DBS in treating other forms of paralysis.

“This foundational work shows the unexpected potential of targeting specific brain regions to restore neurological functions,” said Jordan Squair, a lead author of the study. The team’s innovative methodologies could inspire new treatments for a range of conditions affecting the nervous system.

The implications of this research extend beyond restoring mobility. It represents a shift in how we understand and treat SCI. By leveraging cutting-edge technologies and interdisciplinary collaboration, researchers are uncovering the brain's hidden potential to heal and adapt.

For patients like Jäger, these breakthroughs translate into newfound independence and hope—a reminder of the power of science to transform lives.

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