An implant that delivers electrical stimulation to a select group of spinal neurons can treat dangerously low blood pressure in people with spinal cord injuries, addressing an often "invisible" consequence of paralysis.
For his work in developing this treatment, called the neuroprosthetic baroreflex, Jordan W. Squair is the winner of the 2023 BioInnovation Institute & Science Prize for Innovation. The prize seeks to reward scientists who deliver research at the intersection of the life sciences and entrepreneurship.
"Dr. Squair's prize-winning research on epidural electrical stimulation restores blood pressure control in patients suffering from spinal cord injury," said Yevgeniya Nusinovich, senior editor at Science. "Using this technology to stabilize blood pressure in the normal range decreases patients' risk of fainting and other complications, greatly improving their safety and quality of life."
Squair, a researcher with NeuroRestore at the Swiss Federal Institute of Technology (EPFL), said the treatment offers a new way to address a problem that affects up to 90% of people with spinal cord injuries.
In addition to spinal cord injury, a woman with severe motor and autonomic nervous system disease, who had such low blood pressure that she could not stand for more than a few minutes at a time, was able to walk several hundred meters immediately after receiving the implant and has stopped fainting, Squair wrote in his prize-winning essay in Science.
"Since then it's been a really cool experience to see it work every single time in every person that we've tested," he said. "It's exciting to see a functional neurosurgical approach that works that robustly and that simply."
Spinal cord injury can prevent the brain from modulating blood pressure during posture changes, such as moving to a sitting or standing position. A person's blood pressure can drop to very low levels as a result, which may keep them bedridden, dizzy, nauseous, or prone to fainting.
"Almost all of these patients are being treated for orthostatic hypotension using conservative measures like an abdominal binder, maybe compression stockings on their legs, or they've been recommended to have a high salt diet, things like that," Squair said. "But if you then ask them if they still experience symptoms of it, despite being treated conservatively for it, they almost all still do."
Squair and his colleagues at EPFL and the University of Calgary developed a way to treat this lesser-known consequence of spinal cord injury by expanding the use of epidural electrical stimulation (EES), which has been used in some people to restore movement and sensation.
Neuroscientists Grégoire Courtine and Jocelyne Bloch, who lead NeuroRestore, showed "that if you stimulate a certain part of the spinal cord, you can activate the expected function," Squair said.
Finding the right part of the spinal cord to stimulate was one of the essential first steps in developing the new treatment. Squair systematically tested the spinal cord segment by segment in rodents, combining these findings with anatomical studies. He found that "the best place to stimulate coincides with the place in the spinal cord that contains the most neurons that are relevant for controlling blood pressure."
The last three thoracic segments of the spine are enriched in these neurons. These "hotspots" can be found in mice, rats, pigs, and non-human primates, and have been mapped in some humans, "and they seem to hold up across species," said Squair.
This work is now supported by a large consortium funded by the U.S. Defense Advanced Research Projects Agency (DARPA), to expand the treatment's capabilities. For instance, the implant might be useful in the acute phase of spinal cord injury, when blood pressure can be unstable.
At the moment, this problem is treated with drugs that can overshoot their therapeutic mark or wear off, "so there might be a role for this [implant] to keep people stable when they're in the ICU or spine unit," Squair explained.
Inside the hospital, blood pressure changes are monitored carefully with an invasive arterial line. But when a patient leaves the hospital, "there's not really any way that anyone currently has to monitor blood pressure with that kind of resolution," he said. "So part of the DARPA program is to try to advance that capability, to potentially monitor blood pressure with every beat of the heart."
Clinical trials in collaboration with ONWARD Medical of the implant could begin by next year, Squair said.
"This year's finalists have conducted some truly exceptional research and the standard of all entries was extremely high," said Jens Nielsen, chief executive officer at BioInnovation Institute. "Their work combines cutting edge science with entrepreneurial spirit, aligning with BII's goals of improving human and planetary health."
FINALISTS
Samuel Bakhoum is a 2023 finalist for his essay "Targeting the undruggable." Bakhoum received undergraduate degrees from Simon Fraser University, his Ph.D. from Dartmouth College, and his M.D. degree from Geisel School of Medicine at Dartmouth. After completing his clinical training at Memorial Sloan Kettering Cancer Center (MSKCC) and a postdoctoral fellowship at Weill Cornell Medicine, he started his laboratory in the Human Oncology and Pathogenesis Program and the department of radiation oncology at MSKCC in 2018. His research aims to understand the cellular mechanisms by which chromosomal instability drives cancer progression.
Kaira Wagoner is a 2023 finalist for her essay "Helping honeybees help themselves." Wagoner received an undergraduate degree from Guilford College and her master's and Ph.D. degrees from the University of North Carolina Greensboro. After completing her postdoctoral fellowship at UNC Greensboro, Kaira started her laboratory in its biology department in 2021. Her research focuses on insect chemical communication, pollinator behavioral ecology, and honeybee pests and diseases.
