A novel minimally invasive stereotaxic technique to target inner ear neurons in the mouse

Sensorineural hearing loss (SNHL), a leading cause of disability worldwide, arises from damage to hair cells (HCs) or spiral ganglion neurons (SGNs) within the cochlea. Among its etiologies, auditory neuropathy (AN) is characterized by disrupted signal transmission due to SGN damage. Traditional interventions, such as hearing aids and cochlear implants, provide limited benefit in cases of AN, where neuronal damage impairs signal transduction to the brain. Emerging regenerative therapies, including cell replacement and gene delivery, hold potential to restore SGN function, but their application is limited by challenges in delivering therapeutic agents to cochlear targets. In this study, we developed a novel stereotaxic approach for minimally invasive, precise delivery of therapeutic agents to murine SGNs. Utilizing pre-determined coordinates, we successfully accessed the cochlea and SGNs. Immunohistochemistry confirmed accurate delivery and integration of therapeutic agents. Functional hearing assessments showed that the approach preserved HC function and demonstrated minimal adverse effects. This technique offers a scalable platform for advancing cell and gene therapies aimed at restoring auditory function in AN and other forms of SNHL.