Grant: Project Grant

Myelin is a fatty substance that coats nerve projections for efficient signal propagation. When myelin is damaged, demyelination disorders occur leading to neurological impairments in vision, movement and/or cognition. Demyelination occurs in Multiple Sclerosis (MS), which is known as "Canada's disease" because the country has one of the highest rates in the world with an estimated 100,000 patients. MS is caused by abnormal activity of the immune system whereby the body's own immune cells damage myelin and myelin-producing cells, oligodendrocytes, in the central nervous system (brain and spinal cord). Current MS treatments are disease-modifying drugs that target inflammation and aid patients with relapse-remitting MS, in which episodes of neurological dysfunction are followed by remission. Yet, they are ineffective for progressive MS, which usually evolves from the relapsing stage and involves a continual worsening of the disease with no improvement. Effective treatments for this type of MS would require central nervous system regeneration and remyelination (restoration of myelin). Remyelination can be achieved by forming oligodendrocytes from oligodendrocyte precursor cells in the human central nervous system. However, this process is highly inefficient in MS patients. I discovered that a specific type of neurons (inhibitory neurons) secrete an immunological molecule, called fractalkine, that acts directly on the oligodendrocyte precursor cells in the developing mouse brain and promotes oligodendrocyte formation. This effect could form the basis of much needed future MS therapies. This proposal will determine whether fractalkine regulates remyelination and regeneration in the adult central nervous system using mouse demyelination models. We will determine if fractalkine a) enhances oligodendrocyte formation from precursor cells and subsequent remyelination; and b) modulates interactions between precursors and neighbouring brain immune cells called microglia.