It’s becoming well established from the literature that fat-related metabolism may be disrupted in Friedreich’s ataxia (FA) at the cellular level. Whilst this has been explored in many FA cell types, it is yet to be examined in FA sensory nerves. This is of great importance as these sensory nerves primarily degenerate in FA. Directly relating to this, the Dottori laboratory has generated FA sensory nerves ‘in the dish’ using FA patient stem cells and they have evidence showing their sensory deficiencies, particularly in their ability to sustain a response when exposed to repetitive mechanical stimulation. This deficiency may be dependent on the fat composition of the nerve cell membrane. We propose to explore this further by profiling the lipid compositions in these cell types using a technique called mass spectrometry.
The outcomes of this project will help us understand disease related mechanisms that contribute to the ataxia neuropathology and, importantly, point to potential new therapeutic targets that may halt the progressive degeneration and restore function within the sensory nervous system.