Brain stem cells age faster in patients with multiple sclerosis

A study led by UConn Health has shown that the brain stem cells of the most severe multiple sclerosis patients appear to be much older than the actual age. Premature aging cells have a different role in the brain than normal cells, which may be the key to new treatments for the disease. The study was published in the Proceedings of the National Academy of Sciences (PNAS). 

Multiple sclerosis (MS) is a potentially disabling disease that affects the brain and spinal cord. Due to inflammation and degradation of the insulating layer around the nerve, called the myelin, causes the nerves to transmit signals around the patient's body to be destroyed, and their movement may be difficult. Fortunately, most people with MS have a long period of remission, and when they recover, they can walk and live as they did before the onset.

Over time, most MS patients develop the progressive disease as their condition worsens. Some people actually start with a progressive disease called primary progressive MS.

Currently, there is only one drug for the progressive disease that only slows disease progression but does not stop progress.

In order to find new treatments, Stephen Crocker, a health neurologist at the University of Connecticut, wanted to better understand progressive MS. In the past, he and his colleagues have demonstrated that brain stem cells from people with primary progressive multiple sclerosis can prevent oligodendrocyte maturation. Oligodendrocytes are cells that form myelin. This is what brain stem cells are doing, which may be why patients with primary progressive multiple sclerosis have never been relieved—the insulation around their nerve cells has never been repaired.

Now, Crocker and his colleagues report that brain stem cells from patients with primary progressive multiple sclerosis appear to age prematurely. The research team tested brain stem cells, which, according to standard cell age markers, appear to be decades older than other similar cells from healthy people of the same age.

The team found that brain stem cells in patients with primary progressive multiple sclerosis not only look older but are older. An analysis of the Utah-Jackson Genomic Medicine Single Cell Center Laboratory showed that oligodendrocytes exposed to stem cells in patients began to express different genes. This may explain why the myelin sheath is damaged.

 

Interestingly, the team also found that many of the genes that are activated in oligodendrocytes are stimulated by a specific protein, HMGB1, which is produced at a high level by stem cells from patients with multiple sclerosis. Crocker's labs have shown that when they block HMGB1, oligodendrocytes develop normally.

This protein is effective in preventing the maturation of oligodendrocytes, which was previously unknown. It has been found in lesions and is associated with inflammation, but it is thought to only stimulate the immune system. Now we can see that if we block this protein, we can significantly improve the growth of oligodendrocytes.

Primary progressive MS is a devastating disease, and we still lack effective treatments. Regenerated myelin is a major requirement that is currently unsatisfied. We are pleased to be able to study human stem cells in a culture dish to discover a new disease mechanism that can be addressed in a much-needed treatment for patients with advanced MS.

Researchers believe that understanding the differences between brain stem cells in MS patients and healthy people will provide important clues for the development of much-needed treatments.

Crocker Laboratories also found that treatment of brain stem cells with rapamycin contributes to normal cell development. Rapamycin is a drug that can be used to suppress the immune system. Rapamycin has been tested in MS patients with relapsing remission and found no help. But it may help patients with progressive disease.

Recent studies have shown that drugs aimed at aging processes such as aging may slow the onset and progression of many different chronic diseases, including cancer, atherosclerosis, stroke and Alzheimer's disease, and aging is a major risk for these diseases. factor. This has had a major impact on the clinical treatment of MS because it opens up a whole new direction to explore possible ways to slow disease progression, says George Kuchel, director of the Connecticut Center for Healthy Ageing.

The next step will be to look at brain stem cells from people with relapsing-remitting forms of MS to see if and when these aging-related changes begin. And see if they can be avoided, slowed down or reversed.

Brain regenerative therapies have been in clinical trials and may be adjusted to help rebuild myelin in the nervous system of MS patients. Although MS is not a disease of the elderly, it may be an aging disease. With this in mind, we now want to know how to target this process to strengthen the patient's myelin repair.