Adult neurogenesis for improving urinary function after contusion spinal cord injury

About This Grant

Spinal cord injury (SCI) affects over 300,000 patients in the US, often leading to severe complications. For example, more than 80% of these patients experience urinary dysfunctions, significantly diminishing their quality of life and sense of dignity. No effective treatment exists for these patients, as SCI frequently results in significant and permanent loss of neurons essential for normal functions. Progenitor cell transplantation is currently the most prevalent approach for replacing lost neurons following SCI. While progenitor cell transplantation has advanced to clinical trials, it presents several risks, including immunoreactions, uncertainty regarding the timeframe for transplantation following injury, and ethical considerations. Tumorigenesis is also a major concern with transplantation of cells derived from induced pluripotent stem cells. As an alternative, this project focuses on adult neurogenesis from resident glial cells in the adult spinal cord. This strategy not only generates neurons immune-compatible with the host but also ameliorates the pathological lesion microenvironment. Excitingly, our preliminary results demonstrate that adult neurogenesis promotes bladder function recovery following contusive SCI. Given that clinically relevant contusion SCI often leads to significant neuronal loss, generating a large number of new neurons may be particularly beneficial. Through recent in vivo screens, we identified a combination of transcription factors capable of rapidly inducing substantial neurogenesis from resident glial cells in the adult spinal cord. In this collaborative project, we will first systematically investigate the molecular and cellular mechanisms underlying induced adult neurogenesis after contusive SCI. Next, we will examine the maturation and synaptic integration of these newly generated neurons. Finally, we will assess their role in restoring bladder function post-SCI. Utilizing state-of-the-art technologies, this study has the potential to introduce a paradigm-shifting therapeutic strategy for treating autonomic dysfunction in SCI patients.