Galvani teams with CWRU on hypertension research
by JoJo Platt, contributing editor
August 2022 issue, BioElectRx Business Report
A recent paper in Nature: Scientific Reports provides a peek at what Galvani Bioelectronics and Case Western Reserve University have been up to over the past few years. “Low intensity stimulation of aortic baroreceptor afferent fibers as a potential therapeutic alternative for hypertension treatment” provides an insightful look at an alternative way of using neuromodulation as a means of addressing hypertension and heart failure. But there’s more to the story. A lot more.
As a stand-alone publication, the paper has meaningful and important insights about exploring aortic versus carotid baroreceptor stimulation as a means to address resistant hypertensive patients. CVRx has pursued carotid baroreceptor stimulation while Enopace Biomedical and Sunshine Heart previously explored aortic baroreceptor stimulation to control hypertension and later heart failure—Enopace and Sunshine Heart abandoned their approaches after clinical trial failures.
But stimulation of the aortic baroreceptor still remains largely unexploited. The Scientific Reports authors found that this change in target allowed for significant power saving over the current/voltage amplitude, ultrahigh frequency power-hungry approach of stimulating the carotid baroreceptors.
BBR spoke with Arun Sridhar, a former Galvani executive and co-author of the paper about this and other curiosities surrounding the innerworkings of the heart. “The carotid artery responds to postural changes—what you experience when you sit or lie down,” Sridhar explained. “It increases heart rate and sends everything else in the body, except for the kidneys and the brain, into energy preservation mode. The aortic, on the other hand, drops blood pressure and is part of the “fight or flight” response sending a transient burst to wherever the energy is needed. Think of it like a balloon. The heart gets as much blood as possible and, with a big squeeze, dilates the vessels and delivers a big burst. So, one is posturally dependent and the other gives you what you need in those ‘Oh shit, I have to run away from a tiger,’ moments.”
The research team for the Galvani/CWRU study looked at both carotid and aortic baroreceptors and asked themselves “Why does the power have to always be on? Can one get away with stimulating much less, if so, how?” and secondly “is there any kind of dosing that we can implement to pursue this?” The research team found that they were able to do “micro-cycles” of on for five seconds, off for three seconds, and repeat for a total of 20 seconds. This pattern allowed them to “dose” the stimulation in such a way that you don’t have to keep it continuously on, and you can dose it with lower parameters. This dosing paradigm and its resultant power savings was a primary thrust of the recent publication. But that’s only half of the story.
If you couple the Scientific Reports paper with the patent granted jointly to Galvani Bioelectronics and CWRU, you’ll start to see other elements of the story. Not only were power consumption and dosing considerations, but circadian rhythm also plays a starring role in this saga.
“Neuromodulation of Baroreceptor Reflex” is a patent that capitalizes on the fact that heart failure occurs far more frequently in certain hours of the day than others—specifically between 3:00 and 4:00 am. “This coincidence of timing is no coincidence at all. People’s blood pressure is higher just before they wake up,” Sridhar pointed out. “I asked Steve Lewis, a professor of pediatrics and pharmacology at CWRU and a co-author of the paper, ‘Is there anything that we can do to account for this?’ and he said yes!”
Sridhar went on to explain Lewis’ plan to dose the stimulation in line with the circadian rhythm and stimulate just before the test subjects wake or stimulate immediately before sleep. The 28-day experiment saw interesting results. At day 7, stimulation began—five seconds on, three seconds off—for 30 minutes before the lights came on. The blood pressure showed a meaningful decrease throughout the rest of the day without having to keep the stimulator on the entire time.
“Aortic baroreceptor afferents may be a viable alternative neuromodulation target to carotid baroreceptors stimulation in lowering arterial blood pressure,” the authors concluded. “In hypertension, modulation of aortic baroreceptor afferent activity in order to drive appreciable and prompt reductions in ABP does not necessarily require the use of a high charge injection system or the delivery of the stimulus in a continuous manner.”
Both low-duty cycle stimulation of vagal afferents and intermittent stimulation in early morning (rather than continuously) are well known and accepted in bioelectronic medicine. SetPoint Medical, Medipace, and other companies are already using similar stimulation patterns in their clinical studies.
CVRx received FDA approval in 2019 for Barostim Neo, which uses carotid barostimulation for heart failure. After raising approximately $400 million in investments over the course of nine funding rounds, CVRx closed a successful initial public offering in 2021 and yielded gross proceeds of almost $150 million. The Q2-2022 earnings report filed by the company post higher than expected revenues of $5 million with analyst expectations that it will grow faster than the wider industry.
The intellectual property discussed in the Scientific Reports article was co-developed and remains co-owned by Galvani Bioelectronics and Case Western Reserve University. It’s unclear whether or how soon commercial products will emerge from the technology. But although carotid baroreceptor stimulation enjoys a clearer path to market because of CVRx’s FDA win, the hypertension and heart failure markets are certainly big enough for another novel entrant.