Small companies are finding broad paths to success
While the big medical device makers may have a deep-pockets advantage in the neurostimulation space, many smaller players are innovating their way to advances that offer tantalizing hope for changing patients’ lives.
Two examples from this start-up community, recognized and partially funded by the European Innovation Council, show how small companies can leverage academic collaborations and novel approaches to solve problems once believed intractable—controlling Parkinson’s tremors and routing signals around damaged spinal cords to restore movement in paralyzed patients.
Newronika, which operates under the motto “we transform research into clinical therapy,” saw an opportunity in 2014 to overcome some of the problems with the conventional deep brain stimulation (DBS) currently offered to Parkinson’s patients.
After spinning out from two Italian research institutions—the University of Milan and the Fondazione Polyclinic Hospital—Newronika co-founder Alberto Priori and a team of a dozen other neurosurgeons, neurologists, bioengineers, and neurophysiologists wanted to create a brain electrostimulation implant that could measure neuronal activity and adapt to a patient’s needs moment by moment, akin to a cardiac pacemaker.
Conventional DBS today delivers a fixed, high-frequency pulse of electricity around 130 Hz to a patient’s central nervous system to tamp down the stiffness, slowness (bradykinesia), resting tremors, and coordination issues of Parkinson’s. But the constant rate of stimulation provided by conventional DBS does not address the dynamic nature of the disease’s symptoms. A patient may be fine after taking medication in the morning but suffer severe bradykinesia in the afternoon as the drugs wear off. A different patient may need extra stimulation during an active morning, but little to no stimulation as the day wears on. If their conventional system delivers too much stimulation when it’s not needed, patients can experience severe side effects.
Priori and the Newronika team developed their adaptive system with an external device connected to electrodes implanted in the brain.
“Our first patient had severe dyskinesia (involuntary movement),” Priori said, “but after we adjusted our algorithm we were able to provide a signal that stopped it entirely. He was astonished. And that was our prototype external device!”
After testing the external system on 20 patients, the team worked to create a fully implantable device. The initial patient for that system, shown in Figure 1, underwent implantation surgery in early 2020—just weeks before Covid shut down clinical trials across Europe. Clinical work began again at the end of 2021.
Figure 1. Newronika AlphaDBS system components: there are three main components in Newronika’s system: the AlphaDBSipg implantable device, the AlphaDBSpat patient controller, and the NWKstation that can be programed by a physician. (Photo courtesy of Newronika.)
Ioannis Isaias, Newronika’s chief medical officer and director of the Parkinson Institute in Milan, said the results have been extraordinary. “Newronika uses a linear proportional algorithm—in other words, every minute I measure a brain signal and I stimulate accordingly. No one else can do that.”
According to Isaias, patients who took part in the blind randomized trial—two weeks on conventional DBS alternating with two weeks on adaptive DBS—reported feeling vastly better while using the adaptive pulses. “The device is ready for commercialization,” he said, but it only has regulatory approval for conventional stimulation. The company hopes to receive the CE mark for adaptive mode in the European Union within the next few months.
While the platform ultimately could treat many other conditions—including epilepsy, stroke rehabilitation, or even substance abuse—CEO Lothar Krinke is keeping the focus on Parkinson’s for now. “We’re a small company and while it is a platform that could go elsewhere, we need to focus on this one thing.”
Freelance accountant Luca Santoro, 51, is glad that they have. Diagnosed with Parkinson’s in 2008, he had a conventional DBS device implanted in 2017—but still had to take 48 pills every week to maintain his independence. When he switched to Newronika’s adaptive system last year, he was able to give up medication entirely.
With his 22-year-old son Luca translating from his native Italian, Santoro explained that he was able to walk more than 60 km almost symptom-free during a recent four-day trip to Barcelona—something he wouldn’t have even attempted with his old conventional DBS.
When Onward Medical co-founder Grégoire Courtine was just starting his research career, he began working with young men his age who had suffered spinal cord injuries and could no longer walk.
“Being confronted with these people, who were kind of a mirror image of myself, motivated me to dedicate my research for almost 20 years to finding a way to allow them to walk again,” Courtine said in a video on the company’s website.
He and his team have found a way.
By creating a wireless “digital bridge” around the spine’s damaged region, the company’s technology allows patients’ brains to communicate with long-dormant leg and trunk muscles, allowing them to stand up from their wheelchairs and walk again. Commercialization of this implanted device—called ARC-IM—is several years away.
But the company, recipient of 10 “breakthrough device” designations from the U.S. Food and Drug Administration, expects commercialization later in 2024 of one of those devices, which helped nearly three-quarters of tetraplegia patients—also known as quadriplegia—to reach out, grasp, and pinch objects with long-paralyzed arms and hands.
In a paper published May 20 in Nature Medicine, researchers explain that Onward’s ARC-EX technology (see Figure 2) helped 72% of the Up-LIFT pivotal trial’s 64 participants in 14 countries improve both strength and functionality versus rehabilitative therapy alone. The percentage of successful results increased to 90% when the definition included just a single strength or functional outcome.
Figure 2. During the tetraplegia trial, Onward Medical’s ARC-EX system consisted of electrodes placed at the back of the neck that transmit transcutaneous electrical stimulation to the spinal cord to help restore movement and function in the arms and hands. (Photo courtesy of Onward Medical.)
“The most exciting thing for us is that we’re seeing effects that improve quality of life,” said the publication’s lead author, Chet Moritz, a professor at the University of Washington. “We also believe that the stimulation may be causing neuroplasticity, or in a sense healing part of the damage to the spinal cord injury such that the benefits persist after the stimulation is withdrawn.”
Improvements were seen in patients up to 34 years post-injury, with 87% of the trial’s participants reporting an overall increase in their quality of life, with fewer spasms, improved sleep, and better upper body sensation, including the sense of touch.
“Everyone thinks that with a spinal injury, all you want to be able to do is to walk again,” said study participant Melanie Reid, who broke her neck when she fell from a horse 14 years ago. “But if you’re a tetraplegic—or quadriplegic—what matters most is working hands. There are no miracles in spinal injury, but tiny gains can be life changing.”
It’s not the first big splash the small company has made recently. In May 2023, Onward Medical and its collaborators at the Swiss Federal Institute of Technology and Lausanne University Hospital published a study in Nature describing brain and spinal implant technology that has allowed a 41-year-old man, Gert-Jan Oskam, who was paralyzed from the hips down in a 2011 motorcycle accident, to walk independently. Even when the implants are turned off, Oskam can walk using crutches, indicating he may be experiencing some recovery from his injury.
At a press briefing, Courtine said the system can wirelessly transmit Oskam’s thoughts about moving to a stimulator on his spinal cord to re-establish voluntary movement. “We have created a wireless interface between the brain and the spinal cord using brain-computer interface technology that transforms thought into action,” he said.
Buoyed by encouraging results, Onward Medical is growing their research and development team and planning treatments for more neurological conditions. Currently, however, the company’s core platform remains an investigational device unavailable for commercial use. Their future plans call for both external and internal stimulation platforms, including one that works with a brain–computer interface.
Oskam, who had used earlier stimulation technology to regain some of his ability to walk, said at the press briefing last year that he had felt detached from what the technology was doing on his behalf. “The stimulation before was controlling me and now I’m controlling the stimulation,” he said.
While the technical and clinical challenges in neurostimulation are large, small companies like Onward Medical and Newronika are making great progress pushing the therapy’s frontier to bring patients the promise of a truly better tomorrow.