Researchers have identified a pathway that plays a critical role in whether repair to damaged cells will or will not occur in neurological diseases such as multiple sclerosis. The research provides insight that could lead to new therapies to repair the damage caused by multiple sclerosis.
Multiple sclerosis is an autoimmune disease which is caused by the body’s immune system attacking nerve fibers and the myelin sheath that insulates them in the central nervous system. The damage caused prevents the nerves from ‘firing’ properly, and then leads to their destruction, resulting in physical and intellectual disabilities.
Image: Bundles of neurons, each neuron with a myelin sheath coating.
The two components that are currently thought to determine clinical outcomes in multiple sclerosis are to stop ongoing damage by controlling inflammation in the central nervous system, and to repair the damage that has occurred to the protective myelin sheaths surrounding the nerve fibers.
While several treatments exist to reduce inflammatory damage in multiple sclerosis, no treatments are available to augment the regenerative process called remyelination in which new myelin sheaths are restored to nerve fibers. Critical to the development of such repair therapies is to understand how the brain’s own stem cells can replace the myelin forming cells (oligodendrocytes) lost in the disease. During early stages of the disease the brains own stem cells are surprisingly good at repairing damage in multiple sclerosis. However, for reasons that until now have not been well explained, they become less efficient as the disease progresses.
In this study the researchers have identified the Wnt pathway, which plays an active role in the maintenance and proliferation of stem cells, as a crucial determinant of whether oligodendrocytes can efficiently make myelin. Their studies demonstrate that if the Wnt pathway is abnormally active, then the process is inhibited. This opens up the possibility that the repair can be enhanced in multiple sclerosis patients by blocking the Wnt pathway.
“We believe we have made a significant step forward in understanding why repair might fail in neurological diseases such as multiple sclerosis by identifying a pathway which inhibits the myelin repair process,” said Stephen Fancy, lead author of the study.
References:
1. Stephen Fancy, et al. Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev. 2009, 23: 1571-1585; doi:10.1101/gad.1806309.
