Restores Blood Pressure Balance After SCI

Getting out of bed in the morning without the risk of passing out is a game-changer for 32-year-old Cody Krebs. In 2022, Krebs experienced a severe spinal cord injury (SCI) in a motor vehicle accident. Since that time, Krebs requires the use of a wheelchair. The damage to his spinal cord means his brain can no longer control blood pressure in his body. He was vulnerable to blood pressure drops where he was at risk of losing consciousness, and spikes placing him at risk of a heart attack and stroke.

However, an international clinical trial led by teams at the University of Calgary, École Polytechnique Fédérale de Lausanne (EPFL) and University of Lausanne (UNIL) in Switzerland, and Sint Maartenskliniek, Radboudumc in the Netherlands has given him control again.

"Before the accident, I had no idea how volatile blood pressure can be. Just transferring from my bed to my chair almost knocked me out at times when my blood pressure would drop," says Krebs. "At other times during the day, my blood pressure would spike due to severe nerve pain, causing me to break out in a sweat and experience severe migraines."

Krebs is part of ongoing research at the University of Calgary based on a major discovery to stabilize blood pressure for people with SCI.

In publications in Nature and Nature Medicine, a pair of landmark studies by Dr. Aaron Phillips, Ph.D., UCalgary, Dr. Grégoire Courtine, Ph.D., EPFL, and Dr. Jocelyne Bloch, MD, UNIL, describes the development of a targeted therapy to address blood pressure regulation in 14 participants across four clinical studies conducted at three separate medical centers in Canada, Switzerland, and the Netherlands.

The study participants and Krebs now have an implantable system on their spine consisting of a new class of electrode arrays. These arrays connect to a purpose-built pulse generator—similar to a cardiac pacemaker—that delivers finely tuned electrical stimulation, calibrated to each person's needs. The result is a compact, adaptable system capable of restoring blood pressure stability through targeted neuromodulation that can be controlled through an app.

"Our mechanistic discoveries in Nature were crucial in bridging the gap from foundational neuronal mapping to clinical application. This synergy is what allowed us to move so quickly from theory to therapy," says Phillips, director of the RESTORE Network and associate professor at the Cumming School of Medicine.

"The Nature Medicine study demonstrates several important factors. First, we show that low blood pressure after a spinal cord injury has serious medical consequences that must not be clinically ignored. Second, we show that our neuromodulation therapy for blood pressure instability after SCI can be deployed effectively in diverse clinical settings, at several centers in different countries with different medical protocols."

Phillips adds the Nature paper also showed that long-term use of the therapy treats not only the low blood pressure occurring after SCI but also prevents the development of life-threatening spikes in blood pressure.

"In the Nature study, we were able to identify the entire neuronal architecture of the spinal cord that is responsible for uncontrolled, life-threatening elevations of blood pressure, called autonomic dysreflexia. We also showed that spinal cord stimulation can compete with this neuronal architecture to safely and precisely regulate blood pressure," says Courtine, director of NeuroRestore Center and professor at EPFL.

The results were consistent in study participants across all sites: once activated, the system restored blood pressure to a functional range, often within minutes.

"Based on our experiences with this novel treatment, participants report experiencing less brain fog, having more energy, being able to speak louder, and suffering less from a postprandial dip. In addition, once the surgery was performed by neurosurgeon Erkan Kurt at Radboudumc, this system proved relatively easy to use in their home environment," says Dr. Ilse van Nes, MD, Ph.D., who successfully deployed the system at the rehabilitation center Sint Maartenskliniek in Nijmegen, Netherlands.

"The international deployment shows that the surgery and therapy are safe and effective regardless of local practices. It's a key milestone toward making this technology widely available," says Bloch, neurosurgeon at Lausanne University Hospital.

While much of the focus in SCI care has been on restoring movement, a majority of patients live with chronic hypotension, a condition that leaves them exhausted, cognitively dulled, prone to fainting, and predisposes to cardiovascular disease over the long-term.

"The implanted devices have a robust safety profile, as they are commonly implanted in the treatment of various pain disorders," says Dr. Fady Girgis, MD, neurosurgeon at the Foothills Medical Center. "Therefore, it's an easy transition to implant them for this novel indication. We've seen very impressive and immediate improvements in blood pressure that are evident as soon as the device is turned on intra-operatively."

Krebs says he's proud to be in a clinical trial advancing discoveries in this field. "It feels good to be able to boost my blood pressure when I need to, I have more energy and am thinking more clearly. Also, there are fewer dangerous spikes in my blood pressure. I am very grateful for all the research being done."

The implantable neurostimulation system evaluated in these studies was developed by ONWARD Medical. ONWARD Medical has recently received FDA approval to initiate a pivotal trial of this therapy, which is expected to involve approximately 20 leading neurorehabilitation and neurosurgical research centers across Canada, Europe and the United States.