Neuromodulation is a technique that uses electrical or chemical signals on specific nerve pathways in your body to change the way they carry information. Researchers are exploring a type of neuromodulation called vagus nerve stimulation (VNS) as a way to repair nerve damage in multiple sclerosis (MS).
The defining marker of MS is that it causes damage to myelin, the protective sheath that covers your brain and spinal cord nerves. Without myelin, your nerves can’t transmit messages to and from your body correctly. This can cause issues with your vision, movement, and ability to feel things that come in contact with your body (sensation).
At the 2025 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum in late February, Cristin Welle, PhD, professor of neurosurgery, physiology and biophysics and vice chair for research in neurosurgery at the University of Colorado Anschutz Medical Campus, presented research that suggests there may be a way to repair myelin and get back some of its function with VNS.
Welle says the idea sprung from advances in stroke rehabilitation. VNS through an implant directly on the nerve has been a treatment for depression and epilepsy for decades. In 2021, the FDA approved a paired vagus nerve stimulation device that helps restore upper arm and hand movement following a stroke.
“I was inspired by that work, and my lab began looking at the brain mechanisms that underlie that device in stroke,” says Welle.
Her team partnered with a fellow CU Anschutz lab studying animal models of demyelination. This allowed them to monitor the myelin state inside an animal's brain before, during, and after a demyelinating event.
“We wanted to see if perhaps vagus nerve stimulation could not only drive neuroplasticity, but might have an influence on myelin plasticity and repair,” says Welle.
The Role of the Vagus Nerve
Your vagus nerve has two primary functions in your body. It controls your parasympathetic nervous system. That’s the part of your nervous system that’s responsible for calming your body down: slowing your heart rate and breathing rate, and digesting your food.
When you stimulate the vagus nerve with a mild electric current, it provides a burst of activity into the brain stem. And it's that signal to the brain component that Welle and her team are most interested in.
“We think [it’s] responsible for the changes that we see in myelination and myelin recovery,” says Welle.
Results of Animal Studies
The research started with mice whose DNA had been altered to express a fluorescent protein in the cells that make myelin (oligodendrocytes). By removing a piece of the mice’s skulls and putting a glass window in its place, the researchers could watch what happens over time with these cells as they stimulate the vagus nerve.
For three weeks they fed the mice a toxin that specifically kills oligodendrocytes while imaging their brains every two to three days to see which cells die. Then they stop the toxin.
Welle says the brain already has oligodendrocyte stem cells (precursor cells) that form new cells when the old ones die, but the process doesn’t go far on its own.
“There's a capacity to regenerate oligodendrocytes and myelin, but for whatever reason, both in mice and in humans, after an injury like this, the repair process is not complete, meaning that you only recover about 50% of the oligodendrocytes that you started with,” says Welle.
The team then had the mice learn a new motor task (reaching for food pellets) for seven days. This task by itself encouraged about 15%-20% more oligodendrocyte recovery than in mice that didn’t do the motor task. But in a separate group, mice learned this motor task while having vagus nerve stimulation with every successful reach (called “paired” stimulation). The result:
“They recovered considerably more oligodendrocytes — close to full recovery,” says Welle. “It's strange that you would stimulate the periphery and see this robust effect on myelin recovery in the brain. But that is what we found.”
What This Could Mean for MS Treatment
With this discovery, Welle says the hope is that paired VNS may be able to help people with MS recover more of their oligodendrocytes after a relapse. It would be considered a remyelination therapy, which means it would improve the body’s ability to repair and replace myelin.
“There are disease-modifying therapies (DMTs) like pharmaceutical options that do work well for many patients with MS, but even in those patients, if they are still experiencing relapse, they may continue to have cumulative functional deficits over time due to incomplete repair of myelin,” says Welle. “Because DMTs do not improve the repair process. They only stave off the next relapse.”
Both surgically implanted VNS and the noninvasive version produced these results in animal studies. Welle’s team is launching a clinical study that is enrolling now. The trials will involve four weeks of therapy and a follow-up at six months.
If the trials prove effective, Welle says it’s an exciting and safe new prospect for MS treatment.
“It’s a safe technology, and it can offer benefits that drugs just can't offer right now,” says Welle. “There aren't remyelination pharmaceuticals options on the market, and especially being able to pair with a motor or sensory task is really unique to device technology.”
Show Sources
Photo Credit: iStock/Getty Images
SOURCES:
Cristin Welle, PhD, professor, neurosurgery and physiology and biophysics; vice chair for research, neurosurgery, University of Colorado Anschutz Medical Campus.
Mount Sinai: "What is Neuromodulation?"
Cleveland Clinic: “Multiple Sclerosis," “Vagus Nerve."
McGovern Medical School: "Almost 20 years since FDA approval of vagus nerve stimulation (VNS) for treatment-resistant depression (TRD)."
Frontiers in Medical Technology: "Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy."
News Release, FDA.
