Investigating the potential of Neuregulin-1 in optimizing myelin repair following spinal cord injury

Abstract

Loss of myelin sheath (demyelination) after neurotrauma or myelin diseases such as multiple sclerosis contribute substantially to loss of function and body paralysis in patients. Demyelination is secondary to oligodendrocyte cell death following injury and replacing oligodendrocyte and renewal of myelin (remyelination) are essential therapeutic strategies for improving neurological recovery. Neural stem cells (NSCs) have the potential to replace oligodendrocytes, however, their ability for proper remyelination is limited in the injury environment. In a clinically-relevant model of spinal cord injury (SCI), we have recently identified that chronic depletion of a growth factor namely Neuregulin-1 (Nrg-1) after injury is an underlying cause for inadequate remyelination and that exogenous Nrg-1 treatment can promote oligodendrocyte differentiation of NSCs. In this project, we will combine Nrg-1 therapy with NSCs transplantation to evaluate the potential of in promoting remyelination and improving functional recovery in chronic SCI. Using a variety of approaches including microneurosurgery, stem cell transplantation, in vivo drug delivery, MRI, neurological assessments as well as histopathology, we will evaluate the benefits of this combinatorial therapy for SCI repair. BSc Student Summer Researcher will become a member of our research team and primarily contribute to histolopathological assessments of stem cells transplantation in the injured spinal cord. Impact: Nrg-1treatment is an FDA approved drug with high translational feasibility. It can readily enter the brain and spinal cord tissue and is safe, as it has received approval for a phase II clinical trial for cardiac dysfunction in the US. Furthermore, our proposed strategy can be beneficial for other conditions such as multiple sclerosis, cerebral palsy, stroke and brain injuries.