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METHODS article

Front. Neurol.

Sec. Neuro-Otology

Stereotaxic Inner Ear Regeneration: A Novel Minimally Invasive Technique to Target Murine Spiral Ganglion Neurons

Provisionally accepted
  • 1The Eaton-Peabody Laboratories, The Massachusetts Eye and Ear Department of Otolaryngology - Head and Neck Surgery, Boston, MA, United States
  • 2University of Massachusetts Chan Medical School, Worcester, United States
  • 3Harvard Medical School Department of Otolaryngology - Head and Neck Surgery, Boston, MA, United States
  • 4Department of Otolaryngology, UMass Memorial Medical Center, Worcester, MA, United States

The final, formatted version of the article will be published soon.

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.

Keywords: auditory neuropathy, sensorineural hearing loss, spiral ganglion neurons, stereotaxic surgery, hearing regeneration

Received: 31 Aug 2025; Accepted: 19 Nov 2025.

Copyright: © 2025 Al-Asad, Luu, Edge and Kempfle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Judith S. Kempfle, judith_kempfle@meei.harvard.edu

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