It’s no exaggeration to say that Austin, Texas-based MicroTransponder had a breakthrough year in 2021. In fact, the “breakthrough” nomenclature comes from the FDA, which granted Vivistim System Breakthrough Device Designation and then pre-market device approval in August for its Vivistim Paired VNS device for vagus nerve.
The device uses a small implant in the upper chest with electrodes on the left side of the neck, next to the vagus nerve to improve upper extremity function after ischemic stroke. In addition to FDA approval, it also received the industry publication’s Best New Product of the Year designation Neurotech Reports in Nov. The vagus nerve stimulation (VNS), delivered in small pulses, involves traditional rehabilitation exercises performed under the supervision of a therapist.
The theory behind Vivistim is that the VNS improves the process of neuroplasticity as the rehabilitation exercises of recovering stroke patients rewire the brain. MicroTransponder says the device is “ideal for chronic ischemic stroke survivors who have not regained arm and hand function six months after their stroke and are considered by their physicians to have moderate to severe deficits.”
The fundamental preclinical technology behind the Vivistim has been developed over the past decade at the University of Texas at the Texas Biomedical Device Center in Dallas; MicroTransponder Chief Scientific Officer Navzer Engineer obtained his PhD from the university. One of the center’s researchers, Seth Hays, was working on the technology but has no connection to MicroTransponder.
“There’s an idea that’s been around for decades that if you have a neurological injury, one way you can recover afterward is by directing neuroplasticity, or synaptic plasticity — changes in the circuitry that remains after the injury,” Hayes said. . He and his colleagues chose a VNS-based approach because stimulation of the cervical vagus nerve releases neuromodulators associated with that plasticity.
“The concept behind this was to look at a moment when a patient was doing an exercise,” he said. “At that moment, the circuits that control the arm are active. If you do that together with VNS, you also release the neuromodulators with the idea that it will promote synaptic plasticity in those active circuits.”
The effectiveness of the device, as measured by the Upper Extremity Fugl-Meyer Assessment (FMA-UE), a stroke-specific measure of motor impairment, was demonstrated in a study published in the lancet in April. The FDA approval announcement summarized the results of the study: patients in the treatment group had a mean score increase of 5 points, while patients in the control group had a mean score increase of 2.4 points. In addition, 47.2 percent of those in the treatment group saw a 6 or more point improvement in FMA-UE score 90 days after therapy compared to 23.6 percent in the control group.
The FDA approval allows MicroTransponder executives to launch joint sales efforts, but they are also in the early stages of the strategy to bring the first platform of its kind to market.
“Of course, when you think of new technology coming to market, FDA approval is critical,” said Richard Foust, the company’s chief commercial officer. “The next aspect is really understanding what the state of healthcare is – and that always comes down to how is this being paid for and is there enough need in the market?
“The positive story we have is that today there are CPT codes that talk about a vagus nerve, specifically a cranial nerve. And that gives us a very good foundation for how we’re going to position our product. the store because we don’t have a cover decision, but what we do have is a silence on the decision, so we don’t start with a no cover decision.”
What is ‘Clinically meaningful?’
The launch of the Vivistim also provides an opportunity for the neuroscience community to discuss the implications of existing measures of stroke rehabilitation and how the definitions of functional improvement depend on who is doing the definition. That discussion was sparked in part by a comment in Heart attack in July by Gert Kwakkel, chair of neurorehabilitation at Amsterdam University Medical Center in the Netherlands, and Bruce Dobkin, MD, medical director of the UCLA Neurologic Rehabilitation and Research Program.
Kwakkel and Dobkin said the Lancet The authors’ general interpretation of their results as clinically significant for the effectiveness of VNS could be interpreted as “too optimistic” to call it a new treatment option. However, Kwakkel and Dobkin also introduced a central confounder on how clinically meaningful improvements are defined: “Unfortunately, there is no clear consensus on a definition for a clinically meaningful improvement, also referred to as a clinically important difference, in part because the concept is defined from different perspectives, including clinicians, patients, statisticians, health economists and stakeholders.”
In an email exchange with MD+DI, Kwakkel discussed the amorphous boundaries of what is “meaningful” in stroke rehabilitation: “For example, patients may report improvements in their self-reported well-being following therapy without measurable improvements in their activities and vice versa,” he said. “In the same way, improvement can occur in, for example, a patient’s ability to perform a meaningful task without any improvement in the underlying neurological disorders through the use of compensatory strategies (and vice versa). With that, this core question must always be refined into ‘meaningful improvement in terms of what?’”
“Gert has accomplished something that is at the heart of the whole field,” Hays said. “You could call it a conflict, I guess, but it’s just a discussion of what it means? Surely, families of survivors know what they’ve been through. What does it mean to have something that makes clinical sense? It’s surprisingly hard to define. So some of this will probably be post-hoc – have people found it helpful to them in their lives? And that is a holistic discussion.”
On the other hand, Hays said, self-perceptions of improvement are problematic if a developer wants to bring something to market: “It’s hard to convince the FDA that ‘Hey, these people said this really helped them’ because they’re looking at a quantitative measurement – which of course they need – but a balance will have to be struck between the more qualitative measures and the more quantitative ones.”
A growing market for stroke care
MicroTransponder’s Foust said the dynamics of stroke treatment offer innovative rehabilitation technologies a sizeable market. For example, he said the number of hospitals providing specialist care for stroke has grown from about 500 to more than 2,000 in the past decade, and emergency treatment modalities like TPA delivered in ambulances on the way to the emergency room means more people are surviving strokes.
However, Foust added that the increased number of survivors is not matched by those who are recovering more fully: “It doesn’t appear that the technologies that save people’s lives are reducing limitations,” he said. “They go through a typical rehabilitation regimen and about 50 percent recover and the other 50 percent have varying levels of disability.”
The Vivistim, he said, is for those patients with long-term disabilities who are motivated enough to undergo the implant surgery. The payoff, he said, is that not only can the therapy continue in outpatient rehabilitation centers, but patients can activate the device themselves at home by swiping a magnet on the device up to eight times a day while engaging in daily activities that are important. for them.
“Our technology is special for after they’ve gone through that six-month rehabilitation process because we want to make sure everything that’s available at a lower cost and non-invasive is done. The moment they don’t cross that threshold, there is now another option for them, and that is really the target market.”
And according to Hays, the FDA approval means its use for paired VNS and rehabilitation is in no way limited to stroke; Researchers from UT-Dallas and others are already working on projects to expand its usability.
“One of the important things that came out of the study was that linking VNS to rehabilitation is safe,” Hays said, “and has many applications. There’s no reason it’s limited to stroke. We’re trying it.” now with spinal cord injury patients.Another study we conducted with some collaborators is the combination with cognitive therapy for PTSD.
“The idea is the same, that VNS enhances these neuromodulators and that this actually amplifies the effects of rehabilitation. I think you’re going to see a lot of new applications for something like this appear, probably within the next 10 10 years.”