Grant: Project Grant

In the brain and spinal cord, the tissue is either white matter or grey matter. White matter has its colour because it is enriched in fats due to a structure called myelin. Myelin surrounds the brain and spinal cord nerve fibres, called axons. The purpose of myelin is to speed communication, but also myelin provides food to the underlying axon making it necessary for axonal survival; when myelin is destroyed, often the axon dies as well. Improving myelin regeneration, a process called remyelination is therefore vital not only to restore communication but also to rescue axons in disease conditions. Multiple Sclerosis (MS) is characterized by white matter lesions where myelin is damaged. In these lesions, many axons survive, and in some people, these axons are even remyelinated. However, for the majority of people with MS remyelination is limited. I think improving remyelination may be a way to treat people with MS because those people who have more vigorous remyelination also tend to have less disability. Indeed, recently several medicines are now entering clinical trials to see if they can improve remyelination for people with MS. These medicines work by encouraging the myelin-producing cell, called an oligodendrocyte. While this is an important strategy, these therapies do not foster the local environment where remyelination takes place, which is regulated by immune cells such as microglia and macrophages. In this proposal, we will study the role of microglia and macrophages during remyelination. We will differentiate between these two very similar cell types, we will prevent their activities, and we will study their characteristics during remyelination. We will also develop new tools to understand their features to explore these cells in MS tissue. Ultimately, we wish to understand the beneficial roles of microglia and macrophages so that we can boost these functions and improve remyelination.