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A Mighty Molecule

Posted on February 2, 2019

Can one molecule delay the damage caused by multiple sclerosis?

University of Chicago researchers say yes and have hinged their hope to the tiny molecule Sephin1 and its ability to delay damage to myelin tissue in mouse models.

Myelin is the insulating sheath that surrounds nerve fibers. Myelin plays an important role; it serves as a protective covering for the nerves and also assists in transmitting impulses from one nerve to another.

In the case of multiple sclerosis, the immune system mistakenly sees this myelin covering as a “foreign invader” and attacks it as if it were a bacteria, virus or other germ. These attacks destroy the myelin covering and cause damage to the nerve fibers it once protected.

These attacks wreak havoc on the body and are often disabling; many individuals living with multiple sclerosis live with wide and varied symptoms such as vision loss, difficulty moving, impaired communications, fatigue and pain. Other symptoms include muscle cramping, pain in the eyes, tremors and dizziness.

What symptoms develop and where they develop is largely unpredictable and depends on where the damage occurs to the central nervous system.

For many individuals living with MS, their symptoms come and go.

“Like many autoimmune conditions, individuals living with multiple sclerosis experiences ‘flares’ of their symptoms,” said Dr. Joel Singer, a New York physician.

Flares can last several days or weeks. Symptoms of MS worsen over time, too.

“Currently, there is no cure for multiple sclerosis,” Singer said.

The Chicago study explains how Sephin1 was used to prevent immune system attacks in test mice by delaying the body’s auto-defense system, known as the integrated stress response (ISR), from stopping. By prohibiting the ISR from turning off, inflammation that would kill off myelin-producing cells known as oligodendrocytes is prevented.

The researchers believe their results could mean a new way to treat multiple sclerosis.

According to the National Multiple Sclerosis Society, at least 2.3 million people are living with the condition worldwide, and almost 1 million of those cases are in the United States.

While researchers know about the links between MS and the immune system’s attack on myelin, what they don’t understand is exactly what triggers the immune system to kill off myelin and oligodendrocytes. Some theories include exposure to environmental toxins, low levels of vitamin D and even smoking cigarettes.

While there is no cure for MS, conventional treatments can reduce inflammation attacks on myelin, and oligodendrocytes can help. But, lowering the body’s defense system can leave individuals at risk of other infections.

Other treatments, such as the high blood pressure medication Guanabenz, can cause immune system response in myelin-producing cells, but also has uncomfortable side effects, such as headache, dry mouth and sleepiness. In some individuals, it can also cause a coma.

To effectively stop immune system attacks and not leave individuals at risk of secondary infection, the researchers opted to help cells fight against inflammation and damage cause by the immune system’s response to myelin.

Using Sephin1, a derivative of Guanabenz without its unwanted side effects, can boost the integrated stress response in the myelin-producing oligodendrocytes.

Sephin1 works by prolonging the ISR by blocking a cell pathway that shuts it down, which delays MS symptoms. The researchers also noticed that fewer nerve fibers and oligodendrocytes were damaged. Another benefit was fewer immune system T cells were found in the central nervous systems of the mice.

Additionally, the Chicago team noticed that by protecting oligodendrocytes and slowing down the loss of myelin, there was less “myelin debris” in the mice. The researchers believe that this could reduce immune system response.

Researchers also saw benefits of using Sephin1 in combination with the drug interferon beta, which is often prescribed for those living with MS.


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