Regeneration of Sensory Hair Cells and Restoration of Vestibular Function by Notch Inhibition

Sensory hair cell loss in the vestibular organs of the inner ear causes balance disorders which are essentially irreversible due to the lack of significant hair cell regeneration. Here, we administered a γ-secretase inhibitor to an adult mouse model of vestibular hair cell loss. The treatment resulted in complete regeneration of type II and partial restoration of type I hair cells after one month and restored vestibuloocular reflexes across all frequencies of rotational and linear acceleration. Further recovery was apparent at 8 months. 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.