News Blocking Molecule Prevents B-cells from Entering Brain and Promoting MS Progression, Study Reports Blocking Molecule Prevents B-cells from Entering Brain and Promoting MS Progression, Study Reports by Steve Bryson, PhD | November 19, 2019 Share this article: Share article via email Copy article link Stopping the migration of immune B-cells through the blood-brain barrier by blocking ALCAM, a molecule linked to the progression of multiple sclerosis (MS), lessened disease severity in an MS mouse model, a new study shows. Details of the discovery were reported in the study, āActivated leukocyte cell adhesion molecule regulates B lymphocyte migration across central nervous system barriers,ā published in the journal Science Translational Medicine. The work was led by aĀ team of researchers at theĀ University of Montreal Hospital Research Centre (CR-CHUM)Ā in Canada. MS is characterized by immune cells attacking the myelin sheath, the protective coat around nerve fibers. Normally, cells of the immune system are prevented from entering brain tissue by the blood-brain barrier (BBB), a group of specialized cells wrapped around blood vessels in the brain. These cells tightly regulate the movement of molecules and cells into the brain.Ā Ā The BBB is permeable in people with MS, allowing immune cells such as B-cells (lymphocytes; antibody-producing immune cells responsible for fighting infection) to migrate into the central nervous system (CNS). This contributes to the progressive phase of MS. In an effort to prevent B-cells from entering the brain ā without eliminating B-cells altogether, which are important to the immune system ā the CR-CHUM team identified a molecule on their surface that facilitatesĀ B-cell migration across the BBB. The researchers discovered that by blocking this molecule, the passage of B-cells across the BBB was arrested. The molecule, known as activated leukocyte cell adhesion molecule CD166 or ALCAM, is a protein on the surface of immune cells shown to promote their migration into the brain.Ā Ā Using mice in theĀ experimental autoimmune encephalomyelitis (EAE) model ā that mimics the myelin sheath attack causing MS-like symptoms similar to humans ā the researchers showed that ALCAM is overproduced in B-cells in the CNS of affected mice, and was directly linked to EAE disease progression.Ā Blocking ALCAM ā either by using mice that lacked the ALCAM protein, or mice treated with an antibody that selectively binds to ALCAM and blocks its activity ā the flow of B-cells into the CNS was impaired, and the severity of EAE in mice reduced. Although blocking ALCAM did not affect disease onset, it did slow EAE progression. To determine if blocking ALCAM could be useful to MS patients, the team showed that the migration of human B-cells across the BBB, like in mice, was facilitated by ALCAM, and their migration was inhibited by blocking ALCAM. Analysis of blood and CNS tissue from MS patients also found that the percentage of B-cells with ALCAM, compared to healthy controls, was higher in the patients. “The molecule ALCAM is expressed at higher levels on the B-cells of people with multiple sclerosis. By specifically targeting this molecule, we will now be able to explore other therapeutic avenues for the treatment of this disease,”Ā Alexandre Prat, MD, a neuroscientist and study co-author, said in aĀ press release. “Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyteātargeting therapies for the treatment of MS,” the team concluded. To watch a video showing how blocking ALCAM stopped B-cells from migrating out of blood vessels in the CNS, visitĀ this link.Ā Print This Page About the Author Steve Bryson, PhD Steve holds a PhD in biochemistry from the Faculty of Medicine at the University of Toronto, Canada. As a medical scientist for 18 years, he worked in both academia and industry, where his research focused on the discovery of new vaccines and medicines to treat inflammatory disorders and infectious diseases. Steve is a published author in multiple peer-reviewed scientific journals and a patented inventor. Tags B-cells, BBB, blood brain barrier, central nervous system, EAE, myelin
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