Glial Cell Findings May Alter SCS Market Landscape
by James Cavuoto, editor
January 2020 issue
New findings on the role of glial cells in modulating pain may have a fundamental impact on the market for spinal cord stimulation systems. The topic was one of the major themes at the recent NANS conference in Las Vegas and at least one vendor has invested heavily in the new approach.
In a keynote address at the meeting, Linda Watkins from the University of Colorado described the role that non-neuronal cells such as glia play in the pain pathway. She described how glial cells can interfere with the action of opioids and promote inflammation. She also pointed out that glial cell membranes have different receptors than neurons for Interleukin 1; glial membranes can accept both monomers of the molecule while neurons accept just one. Watkins showed results in dogs where a single intrathecal dose of IL10—an antagonist for IL1—produced significant improvement in mobility nine weeks later.
For vendors of SCS systems, these findings open the opportunity to enhance pain therapy by targeting both neural cells and glial cells with differential waveforms that optimize the response from both targets. Earlier this month, Medtronic announced that it acquired Stimgenics, LLC, a privately-held company based in Bloomington, IL, that has been developing such a therapeutic approach. Stimgenics pioneered a novel SCS waveform known as differential target multiplexed SCS. The therapy, which is delivered via the Medtronic Intellis platform, is believed to engage a novel mechanism that modulates both neurons and glial cells, expanding the understanding of SCS mechanisms of action.
The DTM waveform has been studied in animal models, showing statistically significant reversal of pain behaviors compared to either low frequency or high frequency alone. In addition, preclinical studies investigating the genome of nerve-injured animals suggests that the DTM waveform has a greater impact in the neural-glial interaction than other frequencies alone. Decades of basic science research have expanded the understanding of the role of glial cells in the nervous system, which outnumber neurons 12:1 in the spinal cord. Glial cells are no longer thought to be only “glue” in the brain and spinal cord, but active contributors to neural processing and various disease states including chronic pain.
“Stimgenics’ research is deeply rooted in clinical science that began with animal work more than a decade ago. Our preclinical data demonstrated that the modulation of both neurons and glial cells may return glial cells to their normal state and modify how they interact with neurons, which could normalize biological processes and break the pain cascade,” said Ricardo Vallejo, co-founder and director of research at Millennium Pain Center in Bloomington, IL, and founder and lead investigator of Stimgenics. “I’m thrilled that Medtronic has acquired a therapy that has the potential to significantly improve outcomes for chronic pain patients.”
Stimgenics’ preclinical research on the neuronal-glial mechanism of action has been recognized at various medical society meetings. Over the course of the past two years, the team has received six “best of” awards for their research, three of which were specific to research investigating the DTM mechanism of action. NANS awarded the “Best Basic Science Research Award” to Stimgenics at their annual meeting in both 2018 and 2019.
“Medtronic is committed to providing clinically-proven therapeutic options for millions of patients suffering from chronic pain around the world,” said Marshall Stanton, president of Medtronic’s pain therapies business. “We believe that DTM therapy will advance the treatment of chronic pain, supported by clinical evidence and preclinical research on a neuronal-glial mechanism of action.”
At NANS, Medtronic announced three-month results from a randomized controlled trial of 94 patients showing statistically significant and superior back pain relief with DTM compared to conventional SCS. Both arms used the Medtronic Intellis platform. Three-month results showed 80 percent of patients with chronic back pain treated with DTM reported at least 50 percent pain relief, compared with 51 percent of patients treated with conventional SCS. The trial demonstrated profound pain relief and significant reductions in back and leg pain with DTM.
