Molecular Pathways Modulating Sensory Hair Cell Regeneration in Adult Mammalian Cochleae: Progress and Perspectives

Noise-induced, drug-related, and age-related disabling hearing loss is a major public health problem and affect approximately 466 million people worldwide. In non-mammalian vertebrates, the death of sensory hair cells (HCs) induces the proliferation and transdifferentiation of adjacent supporting cells into new HCs; however, this capacity is lost in juvenile and adult mammalian cochleae leading to permanent hearing loss. At present, cochlear implants and hearing devices are the only available treatments and can help patients to a certain extent; however, no biological approach or FDA-approved drug is effective to treat disabling hearing loss and restore hearing. Recently, regeneration of mammalian cochlear HCs by modulating molecular pathways or transcription factors has offered some promising results, although the immaturity of the regenerated HCs remains the biggest concern. Furthermore, most of the research done is in neonates and not in adults. This review focuses on critically summarizing the studies done in adult mammalian cochleae and discusses various strategies to elucidate novel transcription factors for better therapeutics.