Anti-CD20 Antibodies Reduce Myelin Loss in MS Rats

Treatment with anti-CD20 antibodies reduced the loss of myelin and improved the survival of neurons in a rat model of multiple sclerosis (MS), a new study reports.

The findings imply that B-cells — the immune cells that are killed by anti-CD20 antibodies — play a central role in the development of MS lesions.

The study, “Anti-CD20 treatment effectively attenuates cortical pathology in a rat model of widespread cortical demyelination,” was published in the Journal of Neuroinflammation. The study was funded in part by Roche.

Anti-CD20 antibodies are a class of medication used to treat MS. Currently, two such therapies are approved in the U.S.: Roche’s Ocrevus (ocrelizumab) and Novartis’ Kesimpta (ofatumumab). Both medications are approved to treat relapsing forms of MS; Ocrevus also is approved for primary progressive MS. Other anti-CD20 MS therapies are in development.

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Clinical trials have shown that treatment with anti-CD20 therapies can reduce the rate of MS relapses, lessen the formation of new lesions, and slow disability progression. However, exactly how these therapies affect MS-related damage to the brain remains incompletely understood.

In the new study, a team led by researchers at the Medical University of Graz, in Austria, conducted a series experiments to examine the effect of anti-CD20 treatment on cortical demyelination in a rat model of MS. Cortical demyelination refers to the loss of myelin in the brain. Myelin is the fatty substance that surrounds neurons (nerve cells) like a sheath, helping them to send electrical signals. MS is caused by the immune system attacking the myelin sheath.

The rat model used in the study basically involved administering the animals with a specific protein (myelin oligodendrocyte glycoprotein, MOG) that triggers an MS-like status followed by the injection of pro-inflammatory molecules (cytokines) to prompt the rats’ immune system to launch an attack in the brain, ultimately resulting in cortical demyelination.

The researchers tested the effect of anti-CD20 treatment both before and after this immune stimulation with MOG.

Broadly, the results showed that treatment with anti-CD20 antibodies reduced cortical demyelination in the rat model. A slightly stronger effect was seen when treatment was given before the induction of MS through MOG immunization.

Further investigation showed that mice treated with anti-CD20 therapies had less activation of inflammatory cells in the brain, such as microglia.

“Together, these findings suggest that anti-CD20 treatment prevented cytokine-induced cortical demyelination through suppression of inflammatory responses,” the researchers wrote.

Treatment with these therapies also decreased the amount of neurons that died in the mice’s brains.

“We noted increased neuronal preservation compared to control groups, indicating a favorable impact of anti-CD20 therapy,” the team wrote.

Since anti-CD20 therapies work mainly by killing immune cells called B-cells, these findings support the idea that B-cells play an important role in driving cortical demyelination in MS.

“Our data support the assumption, that anti-CD20 therapy — administered early in the disease course — could reduce, delay or even prevent cortical demyelination, as well as reduce the extent of [neuron] death, thereby promoting neuronal survival,” the team concluded.

The team noted a need for more research to better understand the role B-cells play in the inflammatory attack that drives MS.