Myelin repair early in MS may protect against disability worsening

People in the early stages of multiple sclerosis (MS) who have more spontaneous myelin repair in the cortex — the outermost layer of the brain that’s critical for higher cognitive abilities — are less likely to experience worsening disability, a new analysis suggests.

These findings have important implications for how therapies to promote remyelination might best be used, according to researchers.

A combination of available disease-modifying therapies for MS that reduce inflammation and myelin damage and emerging therapies that promote myelin repair (remyelination) “early in the course of the disease may be most effective in preventing long-term clinical progression in MS,” they wrote.

The study, “Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis,” was published in Brain.

The myelin sheath is a fatty substance that wraps around nerve fibers and helps them send electrical signals. In MS, the immune system attacks myelin, which disrupts nerve signaling and eventually causes nerve cells to sicken and die, leading to MS symptoms and driving long-term disability.

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Some remyelination occurs naturally in MS

Although this general mechanism is pretty well-established, the exact timing and dynamics aren’t. It’s also known that there is some remyelination that occurs naturally in MS, but how this connects with long-term disability outcomes isn’t clear, and few studies have looked at remyelination in the cortex specifically.

In this study, researchers analyzed MRI and clinical data from 140 people spanning all types of MS who were followed for at least five years at centers across Europe. Of note, several of the researchers have financial links to pharmaceutical companies.

All of the patients underwent specialized MRI scans to detect myelin content twice, about a year apart. From these data, the researchers calculated three key variables: the total amount of demyelination (myelin loss) present at the first scan (baseline) compared with a control group of 84 healthy individuals of the same age and sex, and the amount of demyelination and remyelination between scans.

The researchers noted there was a lot of variability in these measurements, but said spontaneous remyelination was “extensive” in half of patients. There also tended to be more myelin loss and less myelin repair at the very edge of the cortex, compared with layers deeper in.

“The outer band of the cortical ribbon displayed a more pronounced extent of demyelination and a lower extent of remyelination compared with the rest of the cortex,” the researchers wrote.

None of the myelin measurements showed clear associations with patients’ age or MS type. Individuals who’d been living with MS for longer have significantly more extensive demyelination at baseline and over time, but the amount of spontaneous remyelination showed no association with disease duration.

“Importantly, our data demonstrate that the extent of cortical remyelination in [people with] MS is not influenced by chronological age, disease duration, or clinical phenotype,” the scientists wrote.

They also noted patients who had more demyelination and less myelin repair over time experienced significantly more atrophy (shrinkage) in the cortex, which is consistent with the idea that myelin damage leads nerve cells to sicken and die.

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40 patients experienced significant disability at 5 years

Over the course of follow-up, 40 of the patients had experienced clinically significant disability at five years. The researchers constructed statistical models looking for significant connections between measures of myelin in the cortex and the risk of disability progression.

Results showed patients with more extensive myelin loss at baseline were significantly more likely to experience a worsening of disability. The models also showed a significant interaction between remyelination, baseline demyelination, and the amount of time patients had been living with MS.

“In other words, a greater extent of cortical remyelination was associated with a lower probability of clinical progression at five years only in the subgroup of [people with] MS with a limited amount of cortical demyelination at baseline and a shorter disease duration,” the researchers wrote.

Based on these findings, the scientists said, if treatments to reduce demyelination and promote remyelination could be given early in the course of MS, it could have “a transformative impact on the evolution of the disease in the long-term, by effectively preventing neurodegeneration and its irreversible clinical consequences.”