The extremely low blood pressure of a spinal cord injury patient can be treated with an implant that sends electrical stimulation to a specific group of spinal neurons, addressing a common “invisible” side effect of paralysis.
Jordan W. Squair will receive the 2023 BioInnovation Institute & Science Award for Innovation in recognition of his work in developing this therapy, known as the neuroprosthetic baroreflex. The award recognizes researchers who work at the intersection of biology and entrepreneurship.
“Dr. Squair’s award-winning research on epidural electrical stimulation restores blood pressure control in patients with spinal cord injury,” said Science senior editor Yevgeniya Nusinovich. “Using this technology to maintain normal blood pressure reduces patients’ risk of fainting and other complications, greatly improving their safety and quality of life.”
According to Squair, a NeuroRestore researcher at the Swiss Federal Institute of Technology (EPFL), the treatment offers a new way to address a problem that affects up to 90% of people with spinal cord injuries.
Squair wrote in his prize-winning essay in Science that 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.
“It’s been a really cool experience since then to see it work every single time in every single person that we’ve tested,” he said. “It’s encouraging to see a functional neurosurgical approach that works so well and so simply.”
A spinal cord injury can prevent the brain from modulating blood pressure when changing positions, such as sitting or standing. As a result, a person’s blood pressure can drop to dangerously low levels, leaving them bedridden, dizzy, nauseous, or fainting.
“Almost all of these patients are being treated for orthostatic hypotension with conservative measures such as an abdominal binder, possibly compression stockings on their legs, or they’ve been advised to eat a high salt diet, things like that,” Squair said. “However, when asked if they still have symptoms despite being treated conservatively for it, almost all of them do.”
Squair and his colleagues at EPFL and the University of Calgary devised a method to treat this less-well-known side effect of spinal cord injury by expanding the use of epidural electrical stimulation (EES), which has previously been used to restore movement and sensation in some people.
Neuroscientists Gregoire Courtine and Jocelyne Bloch, who direct NeuroRestore, demonstrated “that if you stimulate a specific part of the spinal cord, you can activate the expected function,” according to Squair.
Finding the appropriate part of the spinal cord to stimulate was a critical first step in developing the new treatment. Squair tested the spinal cord segment by segment in rodents, combining his findings with anatomical research. He discovered that “the best place to stimulate coincides with the location in the spinal cord that contains the most neurons that are relevant for blood pressure control.”
These neurons are concentrated in the last three thoracic segments of the spine. These “hotspots” have been identified in mice, rats, pigs, and non-human primates, as well as in some humans, “and they appear to hold up across species,” according to Squair.
To expand the treatment’s capabilities, a large consortium funded by the US Defense Advanced Research Projects Agency (DARPA) is now supporting this work. For example, during the acute phase of spinal cord injury, when blood pressure can be unstable, the implant could be useful.
Currently, this problem is treated with drugs that can overshoot their therapeutic mark or wear off, “so this [implant] could play a role in keeping people stable when they’re in the ICU or spine unit,” Squair explained.
Blood pressure changes are carefully monitored inside the hospital using an invasive arterial line. However, once a patient is discharged from the hospital, “there isn’t really any way that anyone currently has to monitor blood pressure with that kind of resolution,” he explained. “As a result, part of the DARPA program is to try to advance that capability, potentially monitoring blood pressure with every heartbeat.”
Clinical trials of the implant, in collaboration with ONWARD Medical, could begin as early as next year, according to Squair.
“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.”