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Stem Cell Research May Mean More Treatment for Myelin Diseases

New findings from Case Western Reserve regarding brain stem cells may yield explanations for the development of conditions that affect myelin in the human body.

Myelin is a fatty substance made up of proteins and phospholipids that serves as a protective sheath, or covering, over many of the body's nerve fibers. In addition to providing protection for the nerves, myelin manages electrical signaling in the brain and is an essential element for normal neurological function.

During the study, Case Western researchers developed a new way to generate oligodendrocyte, the brain cells that create myelin, and the brain stem cells that differentiate into the cells that produce myelin, known as oligodendrocyte pluripotent cells (OPCs), in a laboratory setting. This new method allows scientists to make the cells on a large scale using pluripotent stem cells.

Pluripotent stem cells are adult stem cells that can differentiate into many of the body's different types of tissues.

"Stem cells are the foundation of all the tissues of the body. They are the building blocks on which our bodies are built," said Dr. Bill Johnson, a Dallas, Texas, stem cell physician.

Having a large amount of OPCs available for research gave the study authors more opportunity to study both healthy and diseased tissues of the central nervous system.

To research how myelin affects the nervous system, the Case Western team used genetic models in combination with their cell-creating technology. Their efforts yielded the discovery of a chemical compound that gives affected myelin-making cells the ability to survive.

The research study advances myelin disease research significantly; earlier studies required the creation of mutant mice to investigate the effects of oligodendrocyte dysfunction. Using mutant mice is a lengthy, and often costly, process.

The researchers tested their ability to create oligodendrocyte stem cells to further research Pelizaeus Merzbacher disease (PMD), a fatal genetic disorder that typically affects male children, which causes the death of OPCs as they develop into oligodendrocytes. The condition also affects the part of the cell that processes proteins called the endoplasmic reticulum.

When oligodendrocytes die, myelin does not form properly to protect the spinal cord and brain. As a result, individuals living with PMD develop problems with coordination, motor skills and cognitive function. Most individuals living with PMD die before reaching adulthood.

To prevent the death of the oligodendrocyte cells caused by PMD, the Case Western Reserve researchers found a compound known as Ro 25-6981 that could help protect oligodendrocytes in mouse and human cells affected by PMD.

Now that they have identified how to protect the cells, the next step is determining how they can encourage the rescued cells to create myelin.

The Case Western Reserve research findings span beyond treating PMD; there are scores of neurological diseases caused by loss of myelin tissue or myelin dysfunction. One of these conditions is multiple sclerosis, an autoimmune disease in which the body sees the myelin as a foreign invader and tries to destroy it. Some of the effects of multiple sclerosis include pain, tremors, muscle weakness and rigidity, and fatigue.

Myelin damage and dysfunction is also a consequence of spinal cord injuries and has been linked to schizophrenia.

"The ability to treat conditions caused by myelin dysfunction could mean significant benefits for millions of people," Johnson said.

According to the National Multiple Sclerosis Society, 2.3 million people are living with MS around the world, and 400,000 of them live in the United States. Researchers believe that many more go undiagnosed because symptoms of the condition are not always noticeable.


Sources:

Case Western Reserve University. "More efficiently generating brain stem cells: Technique improves understanding of myelin disease." ScienceDaily. ScienceDaily, 1 October 2018.

National Multiple Sclerosis Society. Multiple Sclerosis FAQs.

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