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Study receives $1.7M to research new therapeutic strategies for MS

A new project aimed at investigating the role of muscarinic type 3 receptors (M3R) in myelination and determining their potential as targets in treating multiple sclerosis (MS) recently won $1.7 million in funding from the US National Institutes of Health (NIH).

The $1.7 million will fund a research team at the University at Buffalo for five years to look at oligodendrocytes – myelin-producing cells of the central nervous system – and the role of muscarinic type three receptors in affecting their activity in MS.

In MS, impaired activity of oligodendrocytes impedes myelin production, leading to degeneration of nerve cell axons and other neurodegeneration. Lack of knowledge about how oligodendrocytes develop and the chemical signalling that controls their maturation are key obstacles in developing therapies for demyelinating diseases, such as MS.

“We will help address this lack of knowledge by studying the function and mechanisms-of-action of muscarinic type 3 receptor in models of human transplant-mediated repair and spontaneous remyelination,” said Fraser J. Sim, PhD, Associate Professor of Pharmacology and Toxicology at the University of Buffalo and the project’s lead investigator. “The results of these experiments are expected to lead to new therapeutic targets for the treatment of demyelinating disease,” he added.

Back in 2016, Sim and his team developed genetic strategies to delete or impair signalling involving M3Rs and showed that these receptors can block oligodendrocyte differentiation, preventing oligodendrocyte progenitor cells from becoming full myelin-producing oligodendrocyte cells. However, the mechanism by which muscarinic receptor signalling blocks oligodendrocyte differentiation is poorly understood, Sim said. Previous research has shown that therapies which block muscarinic receptors improve remyelination and myelin repair in rodents, he added.

The University of Buffalo hope to translate their findings into future therapeutic approaches for MS. The project is titled “Muscarinic Receptor Type 3 Regulation of Oligodendrocyte Progenitor Differentiation.”

Source: MS-UK 10/04/18

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