Brain cells of multiple sclerosis patients age faster and act sooner

Study shows brain cells in multiple sclerosis patients age faster, both structurally and functionally

Brain stem cells in people with the most severe form of multiple sclerosis seem much older than they actually are.

According to a study conducted by UConn Health and published in the journal Proceedings of the National Academy of Sciences (PNAS), prematurely old cells act differently in the brain compared to normal cells. The results could be the key to new treatments for the disease.

Multiple sclerosis (MS) disrupts the ability of nerves to transmit signals throughout the body. MS can make it difficult to walk or hold a pen, for example. The problem is caused by inflammatory and degenerative isolation around the nerves, called myelin. Just like a wire with frayed insulation, nerves with damaged myelin can cause a short circuit or pick up spurious signals. Fortunately, most people with MS have long periods of remission, recover and can walk and live as before the disease develops.

But ultimately, most people with MS develop a progressive illness, in which their symptoms progressively worsen. And some people actually start with a progressive illness, called primary progressive MS.

Currently, there is only one drug for progressive disease, and this slows progression but does not stop it.

Stephen Crocker, a neuroscientist at UConn Health, wants to better understand progressive MS to find new treatments. In the past, he and his colleagues had shown that brain cells from people with primary progressive MS prevented oligodendrocytes, the cells that make up myelin, from maturing. This is something that brain cells do and this is probably why people with primary progressive MS never have remission – the isolation of their nerve cells is never repaired.

The brain stem cells examined by neurologist Anna Williams of the University of Edinburgh, Valentina Fossati of the New York Stem Cell Foundation, and Crocker's lab all seemed to be decades older than cells elsewhere. similar healthy people of the same age, judging by standard age markers cells

Now, Crocker and his colleagues report that brain cells from patients with primary-progressive multiple sclerosis seem prematurely old. The brain stem cells examined by neurologist Anna Williams of the University of Edinburgh, Valentina Fossati of the New York Stem Cell Foundation, and Crocker's lab all seemed to be decades older than cells elsewhere. similar to healthy people of the same age, judging by standard age marker cells.

And the team discovered that not only did the stem cells of the brains of patients with progressive primary sclerosis look old, but they also acted. An badysis by Paul Robson at the UConn – Jackson Laboratory of Genomic Medicine showed that oligodendrocytes exposed to the stem cells of patients begin to express different genes. This may explain why myelin is compromised.

Surprisingly, the research group discovered that many genes activated in oligodendrocytes were stimulated by a specific protein, a protein produced at high levels by stem cells from MS patients. Crocker's laboratory demonstrated that when they blocked this protein, HMGB1, oligodendrocytes then grew normally.

"This protein actively blocks the ability of oligodendrocytes to mature. We did not know it before. It was found in lesions and it was badociated with inflammation, but it was thought that it simply excited the immune system. Now that we can see if we are blocking this protein, we are significantly improving the growth of the oligodendrocyte, "says Crocker.