Multiple sclerosis: Have researchers found a key to prevention?

  1. Mice without calnexin were ‘resistant to MS’

A potential new therapeutic target for multiple sclerosis has now been identified in a new study conducted by researchers at the University of Alberta and McGill University, both in Canada. The results are published in the journal JCI Insight.
Researchers have found that mice that lack a specific brain protein may be resistant to MS.

Multiple sclerosis (MS) is a disease affecting the brain, spinal cord, and optic nerves, symptoms of which can include “cognitive impairment, dizziness, tremors, and fatigue.”

MS severity can vary wildly from case to case. In mild cases, a person might experience minor symptoms such as numbness in the limbs.

Severe cases of MS might result in more serious symptoms — including paralysis or loss of vision — but it is not currently possible for us to predict which cases will progress to this level and which will remain mild.

It is estimated that around 2.3 million people across the globe are living with MS, and the disease is “two to three times more common in women than in men.”

Scientists do not understand the causes of MS very well, but they do know that the disease begins when T cells — which are a type of white blood cell — enter the brain.

When in the brain, T cells attack a protective substance called myelin that sheathes the neurons in the brain and spinal cord, and which helps the nerves to conduct electrical signals.

The T cells erode myelin, resulting in lesions that leave the nerves exposed. As MS lesions become progressively worse, nerves become damaged or broken, thereby interrupting the flow of electrical impulses from the brain to the body’s muscles.

Mice without calnexin were ‘resistant to MS’

In the new study, the researchers examined tissues from donated human brains. They found that the brains of people with MS had very high levels of a protein called calnexin, compared with the brains of people who did not have MS.

The team then used mice that had been bred to model human MS to examine the influence of calnexin in living creatures.

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The study authors were very surprised to find that mice that did not have calnexin seemed to be “completely resistant” to MS.

“It turns out that calnexin is somehow involved in controlling the function of the blood-brain barrier,” explains study co-author Marek Michalak, from the University of Alberta.

“This structure usually acts like a wall and restricts the passage of cells and substances from the blood into the brain,” he adds. “When there is too much calnexin, this wall gives angry T cells access to the brain where they destroy myelin.”

Michalak and colleagues believe that these findings identify calnexin as a potentially vital target for developing future MS therapies.

“Our challenge now is to tease out exactly how this protein works in the cells involved in making up the blood-brain barrier,” adds co-author Luis Agellon, from the McGill School of Human Nutrition.

“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.”

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