Wnt Signalling in Oligodendroglia: A missing link in MS neuroinflammation

Multiple Sclerosis (MS) is the most common acquired chronic neurological disease affecting young adults. In MS, oligodendrocyte membranes, called myelin, are stripped from axons in sporadic autoimmune attacks. This ultimately causes axon degeneration which is irreversible. Currently, we do not have effective therapeutics to help people living with progressive MS. This unmet clinical need is related to the complexity of the pathophysiological mechanisms involved in MS progression.

Our results will demonstrate that CNS immune responses can be abrogated by manipulating intrinsic Wnt signalling within oligodendroglia. We will identify new molecular mechanisms to better understand progressive MS pathophysiology, and identify novel putative therapeutics targets to limit demyelination relevant to progressive MS. In addition, our team has engineered an innovative 3D human induced pluripotent stem cell derived brain organoid. We will use this system to generate new information on how Wnt signalling impacts human de- and re-myelination, and in doing so, demonstrate that our break though 3D human culture system is highly reproduceable and can be used as tool to screen for putative therapeutic compounds. Our ingenuity will significant gap in the pipeline of taking fundamental discovery through to therapeutics that can help people living with MS.