An implant that delivers electrical stimulation to a select group of spinal neurons can treat dangerously low blood pressure in individuals 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 on the intersection of the life sciences and entrepreneurship.

“Dr. Squair’s prize-winning research on epidural electrical stimulation restores blood pressure control in patients affected by spinal cord injury,” said Yevgeniya Nusinovich, senior editor at Science. “Using this technology to stabilize blood pressure in the traditional range decreases patients’ risk of fainting and other complications, greatly improving their safety and quality of life.”

Squair, a researcher with NeuroRestore on the Swiss Federal Institute of Technology (EPFL), said the treatment offers a recent technique to address an issue that affects as much as 90% of individuals with spinal cord injuries.

Along with spinal cord injury, a girl with severe motor and autonomic nervous system disease, who had such low blood pressure that she couldn’t stand for greater than just a few minutes at a time, was in a position 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 has been a very cool experience to see it work each time in every one that we have 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, akin to moving to a sitting or standing position. An individual’s blood pressure can drop to very low levels in consequence, which can keep them bedridden, dizzy, nauseous, or vulnerable to fainting.

“Just about all of those patients are being treated for orthostatic hypotension using conservative measures like an abdominal binder, perhaps compression stockings on their legs, or they have been really useful to have a high salt eating regimen, things like that,” Squair said. “But in case you then ask them in the event that they still experience symptoms of it, despite being treated conservatively for it, they just about all still do.”

Squair and his colleagues at EPFL and the University of Calgary developed a technique to treat this lesser-known consequence of spinal cord injury by expanding the usage of epidural electrical stimulation (EES), which has been utilized in some people to revive movement and sensation.

Neuroscientists Grégoire Courtine and Jocelyne Bloch, who lead NeuroRestore, showed “that in case you stimulate a certain a part of the spinal cord, you may activate the expected function,” Squair said.

Finding the correct a part of the spinal cord to stimulate was certainly one of the essential first steps in developing the brand new treatment. Squair systematically tested the spinal cord segment by segment in rodents, combining these findings with anatomical studies. He found that “the very best place to stimulate coincides with the place within the spinal cord that accommodates essentially the most neurons which might be relevant for controlling blood pressure.”

The last three thoracic segments of the spine are enriched in these neurons. These “hotspots” will be present in mice, rats, pigs, and non-human primates, and have been mapped in some humans, “and so they appear to delay across species,” said Squair.

This work is now supported by a big consortium funded by the U.S. Defense Advanced Research Projects Agency (DARPA), to expand the treatment’s capabilities. As an illustration, the implant could be useful within the acute phase of spinal cord injury, when blood pressure will be unstable.

In the intervening time, this problem is treated with drugs that may overshoot their therapeutic mark or wear off, “so there could be a task for this [implant] to maintain people stable once they’re within the ICU or spine unit,” Squair explained.

Contained in the hospital, blood pressure changes are monitored fastidiously with an invasive arterial line. But when a patient leaves the hospital, “there’s probably not any way that anyone currently has to watch blood pressure with that sort of resolution,” he said. “So a part of the DARPA program is to attempt to advance that capability, to potentially monitor blood pressure with every beat of the guts.”

Clinical trials in collaboration with ONWARD Medical of the implant could begin by next yr, Squair said.

This yr’s finalists have conducted some truly exceptional research and the usual of all entries was extremely high. Their work combines leading edge science with entrepreneurial spirit, aligning with BII’s goals of improving human and planetary health.”

Jens Nielsen, chief executive officer at BioInnovation Institute

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 began his laboratory within the Human Oncology and Pathogenesis Program and the department of radiation oncology at MSKCC in 2018. His research goals to know 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 began her laboratory in its biology department in 2021. Her research focuses on insect chemical communication, pollinator behavioral ecology, and honeybee pests and diseases.

Source:

American Association for the Advancement of Science (AAAS)

Journal reference:

Squair, J. W., (2023). Invisible consequences of paralysis. Science. doi.org/10.1126/science.adg7669.