Grant: Project Grant

Damage to brain white matter occurs following injury and in disorders like multiple sclerosis, and results in a wide variety of neurological issues, including sensory, movement, and cognitive problems. Currently, there are no effective medical therapies to promote brain repair and reduce disability following white matter damage. In this proposal, we hope to change this situation. Brain white matter is comprised of the axons of the nerve cells that conduct information, surrounded by a type of insulation called myelin that ensures signals are sent in a timely and faithful manner. This myelin is made by another brain cell type, oligodendrocytes, and in many of the aforementioned disorders these oligodendrocytes die, myelin is lost, and normal brain information transfer is disrupted. How might we repair this deficiency? Here, we propose a strategy based upon replacing the lost oligodendrocytes, thereby enabling myelin repair and restoration of normal circuitry. To do this, we will take advantage of the fact that our brains contain resident neural stem cells that normally make oligodendrocytes throughout life. We propose to perform studies asking how these stem cells make oligodendrocytes under optimal conditions during development and then to ask if we can recreate these optimal conditions again in the adult injured brain. We will attempt to do this using bioactive agents we define and/or repurposed drugs that we have identified. Ultimately, we hope that these studies will lead to new treatments for human white matter damage.