Cellular Reprogramming by Notch Inhibition Regenerates Hair Cells and Afferent Neurons to Restore the Sense of Balance

Sensory hair cell loss in the vestibular organs of the inner ear causes balance disorders which are essentially irreversible due to the lack of hair cell regeneration. Here, we administered a γ-secretase inhibitor to an adult mouse model of vestibular hair cell loss. The treatment regenerated type I and type II hair cells and restored canal and otolith afferent innervation, resulting in a complete recovery of rotational and translational vestibulo-ocular reflexes across all frequencies. Genetic deletion of Notch1 in supporting cells identified Notch1 as the target of the drug. The results demonstrate that a single injection of a γ-secretase inhibitor is a viable therapy for functional restoration of the vestibular system in patients with balance disorders.