#ECTRIMS2022 – Poor Myelin Repair Offers Clues in Disease Progression

Older MS patients have fewer oligodendrocytes, which corresponds to higher disability

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Remyelination, or regeneration of the myelin sheath that’s progressively damaged and lost in multiple sclerosis (MS), may be less effective for those who develop MS later in life, new research suggests.

People with late-onset MS (LOMS) whose disease appears after age 50 have significantly fewer oligodendrocytes – the cells chiefly responsible for making myelin in the brain and spinal cord – than patients with normal disease onset, results show.

The reduced oligodendrocyte number correlates with greater disability among LOMS patients, which may “partially explain the progressive disease course and the high disability level seen in these patients,” Lidia Stork, MD, of the University Medical Center Göttingen, Germany, said in an oral presentation titled “Reduced oligodendrocyte populations may underlie less effective remyelination in patients with late-onset multiple sclerosis.”

Stork made the presentation at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), Oct. 26–28 virtually and in Amsterdam, the Netherlands.

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A typical MS onset occurs between ages 20–40. When disease symptoms emerge after age 50, patients are considered to have LOMS.

Studies suggest the time of disease onset can influence its course throughout life. For example, LOMS patients are three times more likely to present with a progressive disease course at MS onset with symptoms progressively worsening over time regardless of disease relapses.

These patients also seem to have faster disease progression, poorer relapse recovery, and a worse response to disease-modifying therapies than those with a normal onset.

It’s of significant interest to researchers to better understand what contributes to a more severe disease progression.

The myelin sheath is a fatty covering that helps accelerate the movement of electrical signals along nerve fibers. When myelin in lost — a process referred to as demyelination — nerve cells become more susceptible to damage and nerve communication slows. Ultimately, lesions, or areas of tissue damage and scarring, accumulate in the brain and spinal cord.

Repairing and regenerating damaged myelin by oligodendrocytes is possible to some extent; it occurs in about 23–50% of lesions in people with normal MS onset. The degree of remyelination influences disease outcomes, with a greater remyelination linked to fewer relapses and slower disease progression.

Does impaired remyelination lead to more severe disease?

Stork and colleagues investigated whether a smaller degree of remyelination could explain the more severe disease course commonly observed in LOMS patients.

The research team, funded by Sanofi, used biopsy samples from 30 LOMS patients and 25 patients with normal-onset MS and examined them for markers of oligodendrocytes. Specifically, three types of cells were examined: immature oligodendrocyte precursors, mature oligodendrocytes actively involved in myelination, and mature oligodendrocytes not active in myelination.

Compared with other patients with normal disease onset, LOMS patients had a significantly lower density of mature oligodendrocytes in healthy myelinated tissue – called white matter – and in the tissue surrounding lesions. Likewise, actively myelinating oligodendrocytes were reduced in the white matter of LOMS patients.

Interestingly, the levels of mature and actively myelinating cells were negatively correlated with age, meaning the number of oligodendrocytes decreased as patients got older.

Researchers also examined levels of active myelinating cells within new and older lesions. In early active lesions, cell numbers were similar between groups, but in older lesions, people with LOMS had fewer “active myelinating oligodendrocytes … in the center of the lesion,” Stork said.

As of the last follow-up, LOMS patients had significantly higher scores on the Expanded Disability Status Scale (EDSS) than normal-onset patients, reflecting a greater degree of disability. The higher EDSS scores were correlated with fewer mature and oligodendrocyte precursor cells in active lesions among LOMS patients, but this correlation wasn’t seen in the control group.

The reductions in oligodendrocytes “could influence the efficacy of the reparative process, in particular remyelination, in patients with late-onset MS,” Stork said, noting this could be one factor driving greater disability progression in those patients.

“Therapeutic approaches to improve remyelination are thus necessary,” the researchers wrote.

Note: The Multiple Sclerosis News Today team is providing in-depth coverage of the ECTRIMS Forum 2022 Oct. 26–28. Go here to see the latest stories from the conference.

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