July 26, 2021 | Neuroscientists, neuroengineers, neurosurgeons, and related professionals assembled online earlier this month for the 2021 version of the Neural Interfaces Conference. A spinoff of the original NIH Neural Prosthesis Workshop, this year’s virtual meeting was produced jointly with the North American Neuromodulation Society.
The two-day event kicked off with an NIH/FDA pre-session co-moderated by National Institute of Neurological Disorders and Stroke program director for translational devices Nick Langhals and his predecessor Kip Ludwig, now at the University of Wisconsin. Kari Ashmont, who serves as program officer at NINDS, kicked off the session offering her perspectives on translating medical devices. She encouraged investigators to reach out to NIH program officers in advance. She stressed that NIH programs need to be applicable to a variety of devices, not just a single device.
Other speakers on this session included Megan Moynahan, a former FDA official who is now executive director of the Institute for Functional Restoration at Case, Gene Civillico, who heads up the NIH SPARC program, and Michael Wolfson, program director at the National Institute for Biomedical Imaging and Bioengineering.
Moynahan mentioned some limitations of the FDA’s Q-Submission Program, which lets trial sponsors get feedback from the FDA in advance of submission. If you’re not planning to file an IDE, you might not want to use this, she said. “The FDA is really at its best when it tries to help you get to the next regulatory submission,” she said.
Wolfson described the new Blueprint Medtech program, sponsored by a consortium of 14 NIH centers. Example neurotech research that the program is targeting include circuit disorders, glossopharyngeal nerve stimulation, motor deficits, BCI-controlled robotics, and wearable sensors. “The Blueprint MedTech program is designed to think about the total life cycle—a holistic view of what the product is going to be from concept to obsolescence,” he said. Funding announcements will be made later this summer, with the earliest start date a year from now.
Civillico announced that the NIH will be launching new SPARC initiatives with funding in fiscal year 2022. “What we’re planning to do with the amount of time we have remaining on the SPARC clock is concentrate all this intellectual capital we’ve accumulated in one particular area: the vagus nerve,” he said. Among the forthcoming funding opportunities are a human vagal “subway map,” a multisystem study of existing VNS patients, and open source implantable modules for use in human subjects.
A second pre-session, moderated by NBR senior contributing editor and Neurotech Network founder Jennifer French, was devoted to engaging the target population. The session featured two BCI end users, Ian Burkhart and Robert Chmielewski, and Anita Bajaj, acting assistant director of the Office of Patient Science and Engagement at CDRH. Susan Schaeffer, CEO of the Patients’ Academy for Research Advocacy, spoke about lessons learned in patient engagement from the pharmaceutical industry.
A plenary session devoted to overcoming barriers in clinical neuromodulation featured presentations from Warren Grill of Duke University, Parag Patil from University of Michigan, and Helen Mayberg from the Icahn School of Medicine at Mount Sinai. The purpose of the session was to examine the challenges presented by technology, anatomic diversity, and healthcare delivery that act as roadblocks to expanded penetration of neuromodulation therapies.
Grill spoke about computational models that neuroengineers have used to make the appropriate selection of neurostimulation parameters. He offered two examples as teaching opportunities: Northstar’s failed EVEREST trial of epidural cortical stimulation for stroke, and a comparison of the effects of VNS in rats and in humans. “The myriad challenges to selecting optimal or even effective stimulation parameters for both central and peripheral applications of neuromodulation include a large number of stimulation parameter combinations and stimulation among heterogeneous populations of neurons,” he said.
In the case study of the Northstar trial, Grill noted that only 14 percent of the subjects in the treatment arm received proper dosing, defined as 50 percent of motor threshold. Those patients performed very well compared to the sham stimulation arm and the trial might well have been successful if all the subjects in the treatment arm had been dosed properly. Grill presented a model of epidural cortical stimulation that quantifies thresholds to activate neurons in different locations within the cortex as a function of different stimulation parameters and electrode geometry. The model predicted that if Northstar had used a monopolar electrode configuration, they would have produced a much more widespread region of activation than what was achieved with their bipolar configuration.
Mayberg offered her thoughts on DBS for treatment-resistant depression. One challenge she noted is that we have no biomarkers that define the clinical eligibility to receive DBS. That shortcoming is compounded by the fact that we don’t know target-specific endpoints nor do we know how long DBS in any particular target should take to show its effect, she said.
Mayberg spoke of St. Jude Medical’s BROADEN trial, which produced some promising results even though the trial was halted before it could be completed. She noted that one of the differences between a drug and a device trial is that participants can keep their device and continue to use it after the trial is over. “We’ve found that patients, when they get better, stay better, and we have patients that have been well for 12 to 13 years,” she said.
Mayberg raised the possibility that repeated high-frequency stimulation turns on oligodendroglia progenitor cells that promote remyelination of damaged pathways.
