Millions of people worldwide live with multiple sclerosis (MS), a disease in which the immune system attacks cells in the central nervous system (CNS). MS causes unpredictable symptoms that can include tremors, weakness, vision problems, and fatigue.
Treatments for MS aim to protect neurons by reining in the immune system. This slows progression of the disease, but it also leaves patients more vulnerable to infection.
A discovery from scientists at University of Utah Health suggests an alternative therapeutic strategy: bolstering a natural barricade—the blood-CNS barrier—that breaks down in multiple sclerosis. Ordinarily, this barrier keeps damaging molecules away from neurons.
In mice with an MS-like condition, the researchers found the blood-CNS barrier becomes leaky when the cells that line blood vessels’ interior walls transform and lose the ability to assemble themselves into a tight-knit layer. They found they could restore the barrier by reversing this transformation. Once the barrier was repaired and inflammation-triggering molecules from the blood could no longer enter the CNS, damaged neurons began to recover, and the animals’ symptoms diminished.
Based on previous research, the scientists knew that when the blood-CNS barrier breaks down, the cells that line blood vessels’ walls have often lose the physical junctions that usually link them tightly to their neighbors. This keeps harmful molecules from slipping between them, much like the linked arms in a game of red rover stop advancing runners.
But when they took a close look at the CNS in mice with the MS-like condition, they discovered that the change to those cells went beyond the loss of these structural connections. The cells appeared to have taken on a new identity.
In fact, some of the cells were no longer true endothelial cells, the type of cells that line healthy blood vessels. Instead, they had characteristics of mesenchymal cells, which do not produce the hinge-like proteins that bind endothelial cells together.
Given the critical role of the blood-CNS barrier, the researchers hope that reversing or preventing endothelial cells’ shift to mesenchymal cells could protect the CNS in people with MS—and possibly other neuroinflammatory diseases.