Spinal cord injuries can cut off communication between the brain and neurons that control leg movements, causing paralysis. Despite decades of research, there are very few therapies that can restore the ability to walk afterwards.
For work identifying a novel therapeutic target to improve walking after SCI, Newton Cho is the 2025 winner of the Science & PINS Prize for Neuromodulation. The prize rewards innovative research that modulates neural activity to advance our understanding of human health or to guide therapeutic interventions.
Cho discovered a circuit in the brain that could accelerate recovery after SCI. In his prize-winning essay in Science, he describes how electrical stimulation of this circuit led to long-term improvements in walking in two people with partial SCI.
“The winning essay written by Dr. Cho succinctly and beautifully showcases the potential of neurostimulation for ameliorating spinal cord injury,” said Mattia Maroso, senior editor at Science. “The judges were particularly impressed by the quality of the research, suggesting it could represent an unconventional, paradigm-shifting approach for treating this condition.”
More than just scientific curiosity
For Cho, the drive to find improved therapies for SCI stems from a very personal connection.
“When I was much younger, one of my family members actually suffered a spinal cord injury,” he said. “We as a family saw first-hand the devastating effects of that kind of injury in terms of emotional stress, physical stress, and the economic consequences of it.”
Attempts to treat SCI with neuroprotective drugs or by regenerating parts of the spinal cord have produced mixed outcomes. More recently, combining rehabilitation with electrical stimulation of the lower spine — to activate remaining neural circuits that orchestrate movement — has had some success in restoring walking. Despite these advances, recovery is not always guaranteed or complete.
Looking beyond the spine
Cho wondered if a different approach might be warranted to address this challenge. In his essay, he argues that to improve walking after an injury, scientists must first understand how the brain controls the process.
“Even though the injury is directly to the spinal cord, there are circuits in the brain that are suboptimally activated afterwards,” explained Cho, a surgeon and scientist at the University of British Columbia as part of the International Collaboration on Repair Discoveries . “The ‘normal’ brain as it’s directing walking isn’t necessarily the same brain that’s directing walking after spinal cord injury.”
To trigger walking, the brain sends instructions to neural circuits within the spinal cord, which then activate leg muscles. When the spinal cord is damaged, circuits near the injury site and in the brain undergo reorganization. In less severe cases of SCI —involving partial, or incomplete, severance of circuits — this reorganization can prompt the spontaneous (but limited) recovery of walking.
Cho and his colleagues surmised that an unbiased examination of the entire brain could reveal these pathways and thereby uncover new therapeutic targets to aid recovery. In a 2024 study in Nature Medicine, they tested this theory by performing whole-brain imaging on mice recuperating after SCI.
Unexpectedly, this analysis revealed increased connectivity and activity in a region known as the lateral hypothalamus. Although prior studies have targeted this region to treat other disorders in humans, it had not been previously linked to SCI.
The researchers then stimulated the lateral hypothalamus in different rodent models of SCI. They found that activating a subset of excitatory neurons led to an immediate improvement in walking. Finally, Cho and his team enrolled two people with incomplete SCI in a preliminary clinical trial and observed that deep brain stimulation of the lateral hypothalamus produced long-lasting walking enhancements without causing any serious side effects.
“These achievements have expanded the therapeutic spectrum of neuromodulation. Such progress offers new prospects for neuroscientific research and clinical practice,” said PINS Medical CEO Hao Hongwei.
Being recognized for his work feels like validation for his somewhat unconventional focus on brain circuits in relation to SCI, Cho said.
“It’s good to know that other people feel just as strongly and passionately about what I’m doing, and that I’m on the right path,” he added.
A step in the right direction
Cho is optimistic about what his findings portend for the future of SCI therapies, and notes that larger trials will be necessary to determine efficacy.
He hopes to combine deep brain stimulation with spinal cord stimulation to test whether the two treatments produce complementary effects to restore walking. Cho is also interested in applying lateral hypothalamus stimulation to treat patients with cervical injuries, which occur higher in the spine and impact hand function.
Finalist
Huiliang Wang is a 2025 finalist for his essay, “Rapid deep brain chemogenetics.” Wang received an undergraduate degree from the University of Oxford and completed his Ph.D. and postdoctoral fellowship at Stanford University. In 2021, he started his laboratory at the University of Texas at Austin. His research group focuses on the development of nanomaterials, electronics and genetic approaches for advanced neurotechnology.