A discovery led by a group of researchers from the University of Alberta and McGill University is providing hope for a new therapeutic target in Multiple Sclerosis (MS) patients, which could one day be used to prevent the symptoms and progression of the disease.
Multiple sclerosis is a progressive auto-immune condition that affects the nerves. It happens when the body’s immune cells mistake its own cells as foreign and attack the myelin sheath that covers the spinal cord and/or the brain. This leads to inflammation in small patches known as plaques or lesions that disrupts the messages traveling along the nerves. This causes the impulses to slow down, jumbling them or in extreme cases, stops the nerve transmission completely.
When the inflammation wanes away, it leaves behind a scar on the myelin sheath (sclerosis) that is detectable on an MRI scan. When the inflammation occurs frequently and repeatedly, it leads to permanent damage of the underlying nerves.
While examining donated human brain tissues that were afflicted with MS, scientists found an exceptionally high amount of a protein named Calnexin, compared to normal brain tissues, without MS.
When the researchers tested the susceptibility of mice lacking calnexin to the mouse model of human MS, they were astonished to find that the mice were completely resistant to the disease.
Even though the causes for MS are poorly understood, the problems are generally caused by a type of white blood cells called T-cells that, after becoming activated, find their way into the brain and attack the protective covering—myelin—of neurons in the brain and spinal cord, causing inflammation and damage to the central nervous system.
“It turns out that calnexin is somehow involved in controlling the function of the blood-brain barrier,” said Marek Michalak, a distinguished professor of biochemistry at the U of Alberta. “This structure usually acts like a wall and restricts the passage of cells and substances from the blood into the brain. When there is too much calnexin, this wall gives angry T-cells access to the brain where they destroy myelin.”
“We think this exciting finding identifies calnexin as an important target for developing therapies for MS,” said Luis Agellon, a professor at the McGill School of Human Nutrition.
“Our challenge now is to tease out exactly how this protein works in the cells involved in making up the blood-brain barrier. If we knew exactly what calnexin does in this process, then we could find a way to manipulate its function to promote resistance for developing MS.”
Canada has one of the highest rates of MS in the world, with an estimated one in 340 Canadians living with the disease for which there are currently no known effective treatments.