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Researchers May Have Identified How to Slow the Progression of MS

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Researchers may have identified a way to delay the progression of multiple sclerosis (MS) by blocking a molecule that controls the entry of B cells into the brain, which results in deterioration of tissue.

There is no cure for multiple sclerosis (MS), but researchers at the University of Montreal Hospital Research Centre (CRCHUM) may have identified a way to delay the progression of the disease.

Results published in Science Translational Medicine show that blocking activated leukocyte cell adhesion molecule (ALCAM), which is expressed by B cells, delays the progression of the disease, according to in vitro human and in vivo mouse studies.1 These findings could result in the next generation of therapies to treat MS.

“The molecule ALCAM is expressed at higher levels on the B cells of people with multiple sclerosis,” explained Alexandre Prat, MD-MSc, BSc, a researcher at the CRCHUM, professor at the Université de Montréal and holder of the Canada Research Chair in Multiple Sclerosis. “By specifically targeting this molecule, we will now be able to explore other therapeutic avenues for the treatment of this disease.”

Medications that target B cells have been shown to reduce the progression of MS and disability resulting from the disease. This is the first study to show that ALCAM controls the entry of B cells into the brain and allows them to migrate to the other side of the blood-brain barrier.

“By blocking this molecule in mice, we were able to reduce the flow of B cells into their brains and, as a result, slow the progression of the disease,” Prat said.

The blood-brain barrier is permeable in people with MS, and the migration of lymphocytes into the brain causes the destruction of the myelin sheath that protects neurons.

Treating relapsing MS early and proactively is important before patients’ disease converts to secondary progressive MS, because once it does convert most of the therapies being used have no effect. Research from earlier in the year had identified that using disease-modifying treatments (DMTs) early in patients with MS can reduce the risk of MS progressing.2

The research, published in JAMA, found that patients treated with glatiramer acetate or interferon ß had a lower risk of progression than patients who went untreated, and patients treated with a DMT—such as fingolimod, alemtuzumab, or natalizumab—had an even lower risk of progressing.

References

1. Michel L, Grasmuck C, Carabati M, et al. Activated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers. Sci Transl Med. 2019;11(518). doi: 10.1126/scitranslmed.aaw0475.

2. Brown JWL, Coles A, Horakova D, et al. Association of initial disease-modifying therapy with later conversion to secondary progressive multiple sclerosis. JAMA. 2019;321(2):175-187. doi: 10.1001/jama.2018.20588.

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