Modulation of the Wnt pathway to restore inner ear function

The inner ear relies on sensory hair cells for detection of sound and motion. The loss of sensory hair cells causes hearing loss and balance dysfunction. Because mammalian hair cells do not regenerate, hearing loss and balance dysfunction are irreversible. Current treatment for hearing loss include hearing aids and cochlear implants, and physical therapy for balance dysfunction. These aim at improving the symptoms of hearing loss and balance dysfunction without reversing the underlying problem-hair cell loss. The current research has characterized a signaling pathway, called Wnt signaling, that initiates proliferation and hair cell regeneration, both deemed critical for inner ear regeneration found in non-mammals. Our study found that pharmacologic activators of Wnt signaling can robustly induce proliferation in several group of hair cell progenitors in the mouse vestibular organ, utricle, in vitro. We tested numerous Wnt activators and found one to be most potent in inducing proliferation and also co-activators that further enhance its mitogenic effects. We also identified several Wnt agonists not to be mitogenic, indicating certain Wnt signaling components are absent in the inner ear and underscoring complexity of this pathway previously not appreciated.