Insights into Process of Remyelination May Point the Way Toward Future MS Therapies

Researchers identify a compound released by macrophages following demyelination that may enhance myelin regeneration and hold the key to more effective therapies for patients with multiple sclerosis.

The authors of “M2 Microglia and Macrophages Drive Oligodendrocyte Differentiation during CNS Remyelination,” published in Nature Neuroscience, report that macrophages help trigger the process of remyelination, and that a compound known as activin-A released during this process is associated with increased myelin production.

Researchers studying “an innate immune response consisting of microglia and macrophages, which can be polarized to distinct functional phenotypes: pro-inflammatory (M1) and anti-inflammatory or immunoregulatory (M2),” involved in the process of remyelination found that “a switch from an M1- to an M2-dominant response occurred in microglia and peripherally derived macrophages as remyelination started” in mouse cells and human tissue samples.

They wrote that blocking “M2 cell—derived activin-A inhibited oligodendrocyte differentiation during remyelination in cerebellar slice cultures,” and that these findings indicate that “M2 cell polarization is essential for efficient remyelination and identify activin-A as a therapeutic target for CNS regeneration.”

In a news release from the University of Edinburgh that accompanied publication of the study results, lead author Dr. Veronique Miron, of the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh, said these findings are promising because “Approved therapies for multiple sclerosis work by reducing the initial myelin injury -- they do not promote myelin regeneration. This study could help find new drug targets to enhance myelin regeneration and help to restore lost function in patients with multiple sclerosis.”

According to the news release, scientists are planning further research to look at how activin-A works and determine whether its effects can be enhanced.