Study Receives $1.7M from NIH to Research New Therapeutic Strategies for MS, Others

A new project aimed at boosting the development of new therapies for multiple sclerosis (MS) and other demyelinating diseases recently won $1.7 million in funding from the National Institutes of Health (NIH).
In the five-year study, a research team at theĀ University at BuffaloĀ (part of the State University of New York system) will investigate the role of receptors called muscarinic type 3 receptors in remyelination to determine their potential as therapeutic targets.
In MS, impaired activity of oligodendrocytes ā the myelin-producing cells of the central nervous system ā compromises myelin production, leading toĀ atrophy of nerve cell axons and neurodegeneration.
Lack of knowledge on how human oligodendrocytes develop and the signalling cues that control their maturation are key obstacles in developing therapies for adult demyelinating diseases, such as MS.
āWe will help address these needs by studying the function and mechanisms-of-action of muscarinic type 3 receptor (M3R) in models of human transplant-mediated repair and spontaneous remyelination,ā Fraser J. Sim, PhD, associate professor ofĀ pharmacology and toxicology at the University of Buffalo and the project’s lead investigator, said in a press release.
āThe results of these experiments are expected to lead to the definition and characterization of novel therapeutic targets for the treatment of demyelinating disease,ā he said.
Back in 2016, Sim and his team developed genetic strategies to delete or impair the signalling mediated by M3R, and showed that these receptors can block oligodendrocyte differentiation, preventing them from becoming full myelin-producing cells in both humans and rodents.
āHowever, the mechanism by which MR signaling blocks differentiation is poorly understood,ā Sim said.
Previous research also showed that therapies that block muscarinic receptors improve remyelination and myelin repair in rodents, he said.
The team has now been awarded $1.7 million in funding from theĀ National Institute of Neurological Disorders and StrokeĀ at the NIH to further investigate these signalling pathways, hoping to translate their findings into future therapeutic approaches for MS. The project is titled āMuscarinic Receptor Type 3 Regulation of Oligodendrocyte Progenitor Differentiation.ā
āOur project will establish the therapeutic utility of specifically targeting M3R to improve myelin repair, the mechanisms by which M3R acts to block OPCĀ [oligodendrocyte progenitor cells] differentiation,ā Sim said.
Oligodendrocyte progenitor cells are the cells that give rise to fully mature and myelin-producing oligodendrocytes.
āIn addition to the now-established role of activity-dependent differentiation and myelination, these studies will begin to characterize the novel concept that some neurotransmitters such as ACh [acetylcholine] act to prevent untimely OPC differentiation,ā Sim said.