FKN as a novel remyelination agent: at the interface of cell-to-cell interactions
Summary: Myelin is a fatty substance that protects nerve cells and acts to enhance their signal transmission. MS results from abnormal activity of the immune system whereby the body’s own immune cells target and damage myelin and myelin-producing cells called oligodendrocytes located in the central nervous system. Damage to myelin can result in neurological impairments in vision, movement and/or cognition. There is a need for effective MS therapeutics that regenerate the brain and spinal cord and restore myelin (or remyelinate). Preliminary data indicates myelin formation in developing mice is guided by a molecule called fractalkine. This work will determine whether fractalkine regulates remyelination and regeneration and is a potential target for novel therapies.
Project Description: A hallmark of MS pathology is autoimmune-mediated myelin loss. Disease-modifying treatments exist, but are only effective in treating relapse-remitting forms of MS. One approach to treat progressive MS involves facilitating remyelination by using therapeutics to engage neural stem and precursor cells to produce oligodendrocytes, the myelin forming cells in the brain. This approach may foster new myelin production and ultimately regeneration. Preliminary data from this group has identified that the molecule fractalkine that has been shown to improve central nervous system remyelination by increasing the production of oligodendrocytes. They hypothesize that fractalkine could form the basis of much needed remyelination therapies for MS. This study focuses on fractalkine using a mouse model to determine if it: 1) regulates remyelination and regeneration; and 2) enhances oligodendrocyte formation from oligodendrocyte precursors and from neighbouring brain immune cells, called microglia.
Potential Impact: Results from this work may shed light on the underlying molecular mechanisms involved in brain repair and why remyelination and regeneration is not efficient in people with MS. It will also clarify the role and effect of fractalkine on remyelination and regeneration. If effective, fractalkine could form the basis of remyelination and regeneration treatments for MS.
Project Status: In Progress