Severely low blood pressure in a spinal cord injury patient can be treated with an implant that sends electrical stimulation to a specific set of spinal neurons, addressing the common “invisible” side effects of paralysis.
The 2023 Bioinnovation Institute and Science Award for Innovation recognizes Jordan W. Squires for his work in creating this therapy, called neuroprosthetic baroreflex. The award honors researchers working at the interface of biological sciences and entrepreneurship.
“Dr. Squire’s award-winning research on epidural electrical stimulation restores blood pressure control in patients with spinal cord injury,” said Science senior editor Yevgenia Nusinovich. “Using this technique to stabilize blood pressure in the normal range reduces patients’ risk of fainting and other complications, greatly improving their safety and quality of life.”
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Squire, a neurorestore researcher at the Swiss Federal Institute of Technology (EPFL), said the treatment offers a new way to address a problem that affects 90% of people with spinal cord injuries. With severe motor and autonomic nervous system disease, whose blood pressure was so low that she could not stand for more than a few minutes at a time, she was able to walk hundreds of meters after receiving the transplant and stopped fainting, Squire wrote. His prize-winning essay on science.
“Since then it’s been a really cool experience to see it work every time in every person we’ve tested,” he said. “It’s exciting to see a functional neurosurgical approach that works so robustly and so simply.”
Spinal cord injuries can prevent the brain from modulating blood pressure during postural changes, such as moving from a sitting or standing position. As a result a person’s blood pressure can drop to very low levels, causing them to become bedridden, dizzy, nauseous, or faint.
“Almost all of these patients are treated for orthostatic hypotension with things like an abdominal binder, maybe compression stockings on their legs, or they’re prescribed a high-salt diet,” Squires said. “But if you ask them if they still experience symptoms, despite being treated conservatively for it, almost all of them still do.”
Squire and his colleagues at EPFL and the University of Calgary developed a way to treat this little-known consequence of spinal cord injury by expanding the use of epidural electrical stimulation (EES), which has been used to restore movement and sensation in some people.
Neuroscientists Grégoire Courtin and Jocelyn Bloch, who lead NeuroRestore, “if you stimulate a certain part of the spinal cord, you can activate the expected function,” Squire said.
Trying to stimulate the right side of the spinal cord was one of the first steps necessary in developing the new treatment. Squire systematically examined the spinal cord section by section in rodents, combining these findings with anatomical studies. He found that “the best place to stimulate corresponds to the location of the spinal cord that contains the most neurons relevant to controlling blood pressure.” The last three thoracic segments of the spinal cord are enriched in these neurons. These “hotspots” can be found in mice, rats, pigs, and non-human primates, and some have been mapped in humans, “and they seem to hold across species,” Squire said.
This work is now being supported by a large consortium funded by the US Defense Advanced Research Projects Agency (DARPA) to expand treatment capabilities. For example, transplantation may be useful in the acute phase of spinal cord injury, when blood pressure may be unstable.
At the moment, this problem is treated with drugs that can overshoot or close their therapeutic mark,” so there may be a role for that. [implant] To keep people stable when they’re in the ICU or the spinal unit,” explained Squire.
Within the hospital, blood pressure changes are carefully monitored with an invasive arterial line. But when a patient leaves the hospital, “there’s really no way that there’s any current need to monitor blood pressure with that kind of resolution,” he said. “So part of the DARPA program is to try to advance that capability, potentially to monitor blood pressure with every heartbeat.”
Clinical trials of the implant in collaboration with ONWARD Medical could begin next year, Squire said.
“This year’s finalists have done some truly exceptional research and the standard of all entries was extremely high,” said Jens Nielsen, Chief Executive Officer of the Bioinnovation Institute. “Their work combines cutting-edge science with an entrepreneurial spirit, aligned with BII’s goals of improving human and planetary health.”
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