Auditory neuropathy in mice and humans with Friedreich ataxia

OBJECTIVE: Recent studies have found that human Friedreich ataxia patients have dysfunction of transmission in the auditory neural pathways. Here, we characterize hearing deficits in a mouse model of Friedreich ataxia and compare these to a clinical population. METHODS: Sixteen mice with a C57BL/6 background were evaluated. Eight were YG8Pook/J animals (Friedreich ataxia phenotype) and eight wild‐type mice served as controls. Auditory function was assessed between ages 6 and 12 months using otoacoustic emissions and auditory steady‐state responses. At study end, motor deficit was assessed using Rotorod testing and inner ear tissue was examined. Thirty‐seven individuals with Friedreich ataxia underwent auditory steady‐state evoked potential assessment and response amplitudes were compared with functional hearing ability (speech perception‐in‐noise) and disease status was measured by the Friedreich Ataxia Rating Scale. RESULTS: The YG8Pook/J mice showed anatomic and functional abnormality. While otoacoustic emission responses from the cochlear hair cells were mildly affected, auditory steady‐state responses showed exaggerated amplitude reductions as the animals aged with Friedreich ataxia mice showing a 50–60% decrease compared to controls who showed only a 20–25% reduction (F ((2,94)) = 17.90, p < 0.00). Furthermore, the YG8Pook/J mice had fewer surviving spiral ganglion neurons, indicating greater degeneration of the auditory nerve. Neuronal density was 20–25% lower depending on cochlear region (F ((1, 30)) = 45.02, p < 0.001). In human participants, auditory steady‐state response amplitudes were correlated with both Consonant–Nucleus–Consonant word scores and Friedreich Ataxia Rating Scale score. INTERPRETATION: This study found degenerative changes in auditory structure and function in YG8Pook/J mice, indicating that auditory measures in these animals may provide a model for testing Friedreich ataxia treatments. In addition, auditory steady‐state response findings in a clinical population suggested that these scalp‐recorded potentials may serve as an objective biomarker for disease progress in affected individuals.