Slowly expanding MS lesions linked to myelin damage in brain
Myelin loss seen throughout brain regions, study finds
In people with multiple sclerosis (MS), lesions that get slowly bigger over time, potentially due to chronic inflammation, are associated with more myelin loss throughout the brain, a study found.
Loss of myelin was observed in these slowly expanding lesions, in other types of lesions, and also in regions of the brain that were seemingly normal.
The data suggest that newer, more powerful MS therapies such as Ocrevus (ocrelizumab) can more effectively limit this myelin loss.
The study, “Presence of slowly expanding lesions in multiple sclerosis predicts progressive demyelination within lesions and normal-appearing tissue over time,” was published Multiple Sclerosis Journal.
MS is caused by inflammation in the brain and spinal cord that causes damage to the myelin sheath, a fatty covering around nerve fibers that helps them send electrical signals. In MRI images of the nervous system, areas of MS-related damage are visible as spots known as lesions.
MS lesions and myelin damage
Slowly expanding lesions, or SELs, are lesions that are getting progressively larger over time. SELs have been linked to a higher risk of MS disability progression.
Researchers have thought that these lesions represent areas of chronic active inflammation, meaning they would theoretically be associated with more myelin damage, but there hasn’t been much data on how SELs are related to myelin damage over time. It also hasn’t been clear if the presence of SELs affects myelin damage in other parts of the brain.
Seeking to better understand the relationship between SELs and myelin damage, researchers conducted an analysis of imaging data that was acquired as part of OPERA II (NCT01412333), a clinical trial that helped support approval of the MS therapy Ocrevus. The study was funded by Roche, the company that sells Ocrevus.
The researchers analyzed imaging data from 50 MS patients, 33 of whom had at least one SEL. The patients were followed for up to four years.
Analyses of myelin-focused imaging indicated that rates of myelin loss in SELs were significantly higher than in non-SEL lesions. Among patients who had SELs, other lesions that were not SELs showed higher rates of myelin loss over time compared with lesions in patients who did not have SELs.
This finding “suggests that the occurrence of one or more SELs may be indicative of a widespread inability to resist more severe focal tissue damage,” the researchers wrote.
Data also indicated that patients with SELs had more signs of damage over time in normal-appearing parts of the brain. Overall, the data are consistent with the idea that SELs are associated with more chronic inflammation and myelin loss, not just in the SELs themselves but also in other parts of the brain.
“SELs and other brain tissue in participants with SELs appear to be experiencing ongoing demyelination, presumed due to smouldering or chronically active inflammation within SELs and globally, which could be a factor in MS progression,” the researchers wrote.
In the OPERA II study, patients were given either Ocrevus or a less-effective MS therapy called Rebif (interferon beta-1a). Findings from the main study had shown that Ocrevus was better than Rebif at preventing disability progression. Analyses of available imaging data indicated that SELs from Ocrevus-treated patients showed less myelin loss over time than SELs from patients given Rebif.
“The differences favouring [Ocrevus] over [Rebif] are in agreement with the overall OPERA study results showing improved outcomes for [Ocrevus]-treated participants on clinical measures (lower risk of confirmed disability worsening) and MRI measures (brain atrophy) associated with progression or disease worsening,” the researchers wrote.
These data suggest that newer, more powerful therapies may help reduce SEL-related damage, though the researchers cautioned that this analysis included only a few dozen patients, so further studies are needed to validate the results.
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