Measuring the speed of signals sent to the brain by nerves in the eye could help assess if remyelination is taking place, a study in cats suggests.
Such measurements could be useful in evaluating multiple sclerosis (MS) treatments aiming to repair myelin in clinical trials — of particular interest to people with progressive MS, who have few therapy options, its researchers said.
The study, “Evoked potentials as a biomarker of remyelination,” was published in the journal PNAS.
Myelin is a protein that surrounds neurons like a protective sheath, allowing them to send electrical signals faster and more efficiently. In MS, the immune system attacks myelin, ultimately leading to disease symptoms.
Interest is growing in therapies that might promote remyelination — the recovery of myelin. But confirming the presence of myelin in the central nervous system, important in evaluating potential treatments, requires taking samples of nerve tissue. That’s too invasive and damaging to be a feasible approach for patients.
Researchers at the University of Wisconsin-Madison demonstrated that remyelination could be assessed using a non-invasive test called visual evoked potential (VEP).
VEP is a measurement of the electrical signal recorded through the visual pathway in response to a light stimulus. It involves giving a person a flash of light to the eye, which triggers an electrical signal that travels from the eye’s retina through the optic nerve until it reaches the brain. Using electrodes on the person’s scalp, it is possible to measure the specific brain activity resulting from the flash of light stimulus.
The time lag between the light flash and the brain activity is called latency.
“When that latency increases, it’s taking longer for the signal from the lights to get from the retina down the optic nerve to the brain,” Ian Duncan, PhD, co-author of the study, said in a news story. “As MS progresses and demyelination of axons in the optic nerve worsens, the latency grows.”
“If we could prove that a decrease in latency in the VEP truly reflected remyelination of nerve axons, then you’d have it,” Duncan added. “You’ve got a way to tell if there’s improvement in a patient, an outcome measure that can show whether the drug you are testing is successfully promoting myelin repair.”
In the study, researchers used a feline model of MS to test their hypothesis.
When cats are fed irradiated food, they undergo substantial myelin loss, including in their optic nerves. But when returned to a normal diet, cats recover the lost myelin (remyelination). The researchers took VEP measurements throughout this process, and compared these measurements to nerve samples.
They found that, indeed, VEP latency correlated closely with the loss of myelin and its recovery.
“The normal latency of the VEP in the cats is between 50 to 60 milliseconds,” Duncan said. “At the height of disease, it goes up to 90 to 110 milliseconds. And then, at recovery, it comes back down to around 60 to 70 milliseconds.”
Duncan noted that the latency does not fully recover, because the myelin newly formed is thinner than it was prior to being damaged. But “thin myelin is enough to restore function and sufficient to protect nerve fibers in the long run,” he said.
An analysis of tissue samples confirmed the formation of new myelin along nerve axons as the VEP latency time decreased.
“VEP can be used as an outcome measure in future MS trials in which remyelination is the goal,” the researchers concluded based on these findings.
“If you’ve got a drug to promote myelin repair in MS patients, we now have a proven outcome measure,” Duncan said. “VEP can accurately quantify the drug’s remyelinating effect in the optic nerve — likely reflecting remyelination throughout the central nervous system — and can help begin to sort the wheat from the chaff in potential remyelinating therapies for people with progressive MS.”
