Endogenous cell replacement: progenitor characterization and promotion of oligodendrocyte differentiation and remyelination in the central nervous system by attenuating myelin inhibition

White matter is the part of the nervous system composed mainly of nerve fibres covered by a lipid-dense sheath of myelin. Myelin is produced by cells known as oligodendrocytes, and is responsible for increasing the speed of electrical impulses throughout the nervous system. White matter disorders, such as multiple sclerosis (MS) and spinal cord injury (SCI), comprise a devastating group of conditions that affect millions of people around the world. Although these disorders may have different features, they are all characterized by myelin damage that will not sufficiently repair (remyelinate). While the exact cause of this insufficient remyelination is unknown, one thing is clear: for myelin repair to occur, oligodendrocyte precursor cells (OPCs) need to proliferate and migrate to areas of demyelination, to differentiate, and to then remyelinate denuded neurons. While the transplantation of cells with the potential to myelinate is feasible, there are significant barriers for effectively translating this technology into clinical treatment. An alternative strategy is to activate precursor cells within the host tissue (endogenous cells) to mobilize and promote repair. Jason Plemel was previously funded by MSFHR for his work studying oligodendrocyte transplantation following spinal cord injury. He is now exploring the dynamics of cell-based repair via endogenous cells. He is studying the capacity of oligodendrocytes to self-renew and replicate under normal and disease conditions. He is also investigating possible inhibitory signals at the region of damage that could inhibit endogenous repair, and whether these signals could be blocked to promote remyelination. Plemel anticipates that this work could ultimately lead to new targets for drugs that promote regeneration of myelin in a number of white matter disorders.