The human central nervous system largely lacks neuro-regeneration capabilities, making it difficult to repair once damage is done. Both spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) affect a significant population across the world; motor neuron damage leaves patients of both conditions with some degree of motor deficit, paralysis, or even death. Previous research demonstrated that the overexpression of certain transcription factors, such as NeuroD1 (ND1), can trans-differentiate mature astrocytes into mature, functional neurons. The following thesis looks to build upon the field of direct cellular reprogramming, applying the technology to SCI and ALS mouse models. Along with ND1, the transcription factors, Isl1, Lhx3, and Ngn2, are thought to promote motor neuron differentiation. Through histological analysis, we were able to demonstrate the overexpression of virally introduced NIL (Ngn2, Isl1, Lhx3) transcription factors in a SCI mouse model, potentially resulting in astrocyte-to-neuron differentiation. Furthermore, evaluation of physical and behavioral parameters in the SOD1-G93A mouse model of ALS revealed significant beneficial effects of astrocyte-to-neuron conversion by virally introduced transcription factors ND1 and Isl1. While the results are promising, much work still needs to be completed in order to prove the validity and efficacy of the potential therapeutic treatment.
