The blood-brain barrier in healthy people is a powerful shield that protects neurons from harmful invaders. But in people with multiple sclerosis (MS), that shield malfunctions, allowing B cells from the immune system to pass into the brain and destroy healthy tissues.
Scientists at the University of Montreal Hospital Research Centre (CRCHUM) have identified a new target that they suggest could be exploited to slow down the flow of B cells into the brains of people with MS. They reported the discovery in the journal Science Translational Medicine.
B cells produce a substance called activated leukocyte cell adhesion molecule (ALCAM) that allows them to migrate into the brain via blood vessels, the researchers found. Blocking ALCAM in mouse models of MS reduced the flow of B cells into the brain and slowed the progression of the disease, they reported.
B cells are a major culprit in progressive MS, the most severe form of the disease, and there are drugs on the market designed to deplete them, including Roche’s Ocrevus. Novartis is in phase 3 trials of Arzerra (ofatumumab), a drug that eliminates B cells by binding to the surface protein CD20. Arzerra is approved to treat chronic lymphocytic leukemia, but Novartis has been gunning for a bigger market opportunity. In September, it released new phase 3 data showing that Arzerra reduced MS relapse rates by more than 50% when compared to Sanofi’s Aubagio.
Meanwhile, several academic teams are looking to genetics as a path to personalized MS treatment strategies. In October, researchers at Johns Hopkins reported that newly discovered variants in the genes C1, CR1 and C1QA are associated with vision loss in progressive MS. They believe further research into these “complement genes” could lead to the development of new MS therapies.
Blocking ALCAM could also offer a promising strategy for thwarting B cells in MS, said University of Montreal Professor Alexandre Prat, Ph.D., in a statement. "The molecule ALCAM is expressed at higher levels on the B cells of people with multiple sclerosis,” he said. “By specifically targeting this molecule, we will now be able to explore other therapeutic avenues for the treatment of this disease."