Multiple sclerosis (MS) is a devastating neurological disorder that is thought to be caused by a problem with the immune system. MS causes the body to attack myelin, the fatty tissue surrounding nerves. When this happens, nerves cannot function. MS attacks the central nervous system, which is the brain, the spinal cord, and the optic nerves. It's estimated that there are 2.3 million MS patients worldwide and the number is growing.
With no known cause and no cure, it's a primary focus of many research studies. There are two types of MS, relapsing and remitting, where patients have attacks of more severe systems, alternating with periods of remission from the disease. Primary progressive MS is more dangerous, in that form, the disease does not go away and progresses rapidly to severe impairment.
Scientists from the University of Alberta and the McGill University have published research that shows a particular protein that is present in higher levels in patients with the disease when compared to healthy individuals. The absence of this protein could spur research that targets it, and hopefully, from there, treatments can be found.
The finding came as a bit of a surprise as the amount of calnexin, the protein they found in high levels n MS patients, was not the initial focus of the work. With such high levels in all of the MS brains that were being examined, investigating in a mouse model was the next natural step for the study. If there were mice that did not have this protein, would that have a protective effect against MS?
Mice that lack the protein can be bred, and in the research, these mice were then given immunizations of antigens derived from the CNS. These antigens cause typical mice to acquire the mouse version of MS, which is called experimental autoimmune encephalomyelitis (EAE.) The team also had a control group of mice that were typical, and that group was also induced with EAE. In the mice that lacked calnexin, there was resistance to the disease. T cells, which are white blood cells, are responsible for carrying MS to the brain and these cells appear to be activated by the massive amounts of calnexin
The causes of MS are not well understood. Symptoms vary widely but often include cognitive impairment, dizziness, tremors, and fatigue. These problems are 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.
Marek Michalak is a professor of biochemistry at the University of Alberta and explained the work, writing, "It turns out that calnexin is somehow involved in controlling the function of the blood-brain barrier. 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." Michalak's colleague on the work, Luis Agellon from McGill University added, "We think this exciting finding identifies calnexin as an important target for developing therapies for MS. 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 is particularly affected by MS, with one of the highest rates of the disease in the world. One in 340 Canadians has MS so research there is crucial. The Multiple Sclerosis Society of America has designated March as Multiple Sclerosis Awareness Month. Check out the video below to learn more about this disease.
Sources: Sources: JCI Insight, University of Alberta, MSAA
