Investigating Proprioceptor Development and Function in Friedreich’s Ataxia

A deficiency in proprioception, the perception of the body position and movement, is one of the earliest symptoms observed in Friedreich Ataxia (FA). The loss of proprioception is associated with prominent neurodegeneration in proprioceptor sensory neurons and within the cerebellum. A major question in FA research is when does the proprioceptor impairment start, and what is the mechanism underlying this in terms of having reduced Frataxin expression. There is some evidence to suggest that the defect in proprioceptor function is genetically determined rather than progressive post-symptom onset. Other studies have reported that increased Frataxin levels are associated with proprioceptor/sensory neuronal differentiation, suggesting that low frataxin levels may impact proprioceptor development. This project aims to understand the neurodevelopment and neurodegenerative changes of FA and their implications for pathogenesis and therapies. Specifically, Dr. Dottori will use stem cells generated from FA patients to produce proprioceptor neurons as a model to investigate the mechanisms underlying proprioceptor dysfunction in FA. This is a necessary first step to determine ‘when’ and ‘how’ FA proprioception deterioration begins and when and how this can be halted and/or rescued by increasing Frataxin expression and determine the appropriate timing of treatment.