Wayne State professor wins grant to study oligodendrocytes in MS

Project targets role of Trb3 in nerve cell damage

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by Margarida Maia, PhD |

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Alexander Gow, PhD, a professor at Wayne State University School of Medicine in Detroit, has been awarded a grant to study how stressed oligodendrocytes, the cells that produce myelin in the brain and spinal cord, could be at the origin of multiple sclerosis (MS).

The three-year, $644,827 grant from the National MS Society will support a project titled “Metabolic stress and oligodendrocyte pathophysiology.” The funds will be used to better understand the role of Trb3, a protein produced in response to stress, and whether that protein can be targeted to help prevent nerve cell damage or promote repair in MS.

MS is caused by an overactive immune system attacking the protective myelin sheath that wraps around nerve fibers, which causes damage to the brain and spinal cord.

While damaged myelin can normally be restored by oligodendrocytes, specialized support cells that produce this fatty substance, these cells are typically abnormal in MS and cannot repair the damaged myelin as effectively.

“MS is commonly defined as a primary autoimmune disease,” Gow, associate director of Wayne State’s Center for Molecular Medicine and Genetics, said in a university press release. “However, at diagnosis, many patients show previous disease activity in MRI scans.”

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‘Mini-brain’ models point to poorer oligodendrocyte growth in PPMS

Trb3 may be ‘good drug target’

Growing evidence suggests that many patients go through a period called a prodrome, in which they experience a combination of unspecific symptoms that sometimes begin years before more obvious, disease-specific symptoms appear and a diagnosis can be made.

Because MRI scans show “previous disease activity” in many patients when they are diagnosed, disease may begin as long as “a decade or two” before it’s discovered, “so no one knows how it starts,” Gow said. “Maybe it is autoimmune, but maybe something else leads to autoimmunity,” he said. “This broader perspective of MS is central to us.”

Metabolic stress also is believed to contribute to nerve cell damage and disease progression in MS. This type of stress may arise from a variety of issues, including a lack of energy to supply the cell’s ongoing demands or failure to break down and recycle flawed proteins.

Earlier work by Gow’s team, also funded by the National MS Society, has demonstrated that the Trb3 protein found in oligodendrocytes can ease metabolic stress, leading to milder disease symptoms in animal models of MS.

“We have identified a protein in oligodendrocytes, called Trb3, that might be a good drug target for this,” Gow said. “In this project we will test whether Trb3 can reduce disease in [oligodendrocytes]. We will also characterize two other proteins that interact with Trb3 because they are known to control metabolism in cells.”

Gow’s new project will use mouse models to see how deleting each of those proteins affects metabolic stress or myelin production. The results may be used to identify small molecules with the potential to prevent or repair nerve cell damage.

“Dr. Gow’s research is an excellent example of how Wayne State University is playing a vital role in the health of Detroiters and people around the world,” said Ezemenari Obasi, PhD, vice president for research at Wayne State University. “Dr. Gow’s important work has the potential to provide new insight into a disease that affects nearly one million people in the United States.”