Spinal cord injury (SCI) and Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig’s disease, are both highly debilitating afflictions of the spinal cord with limited available therapies. Pathology is comparable to that of other central nervous system (CNS) injury and disease, involving neuron degeneration and reactive gliosis, which prevents axonal recovery and results in a glial scar. Since the invention of induced pluripotent stem cell technology, many studies have demonstrated direct trans-differentiation across cell lineages through the upregulation of developmental transcription factors. Previous work, including ours, has shown that upregulation of neural transcription factor NeuroD1 can directly convert astroglial cells into neurons in the brain. Through cell culture and mouse models for SCI and ALS, this technology is applied to the spinal cord to regenerate spinal cord neurons from the glial scar. This thesis aims to demonstrate the potential of improved functionality and quality of life after injury by reprogramming reactive astrocytes in the spinal cord into neurons.
