The Potential Of A Stem Cell-Based Therapy To Reverse Neurodegeneration From Spinal Muscular Atrophy

Spinal Muscular Atrophy is a devastating neurological disease that primarily damages motor neurons, but has pathological impacts throughout the body. While current treatments of SMA can prevent further deterioration, a therapy to reverse motor neuron degeneration has not been developed. Stem cell-based transplantation offers the potential to replace lost neurons and reinnervate skeletal muscles, creating a degree of disease amelioration higher than ever before possible. Neural stem cells can provide neuroprotection to endogenous motor neurons through the secretion of neurotrophic factors while differentiating into a small number of motor neurons in vivo. They can be effectively cultured from pluripotent stem cell sources for transplantation. On the other hand, neural stem cells can also be differentiated into motor neurons in vitro and then directly injected into spinal cord parenchyma. However, various challenges must be overcome for this treatment to reach its full therapeutic potential. Overall, in animal models, cell migration to areas of neurodegeneration has been limited, and engraftment may be further hindered by signals from the spinal cord microenvironment, especially in a neurological disease such as SMA. Additionally, axon growth from transplanted cells is restricted and does not result in significant neuromuscular junction formation. There are potential solutions, however, such as alleviating inflammatory glial signals through SMN protein correction using current SMA treatments, thus increasing the engraftment rate, or enhancing axon elongation through hindering effects of myelin proteins using rolipram. Further research is needed to overcome these issues for significant motor function restoration in SMA patients.