A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils

Tziridis K, Rasheed J, Kwiatkowska M, Wright M, Schlingensiepen R (2025)

Publication Type: Journal article

Publication year: 2025

Journal

International Journal of Molecular Sciences MDPI

Book Volume: 26

Article Number: 5124

Journal Issue: 11

DOI: 10.3390/ijms26115124

Abstract

A single intratympanic application of the small-molecule drug AC102 was previously shown to promote significant recovery of hearing thresholds in a noise-induced hearing loss model in guinea pigs. Here, we report the effects of AC102 to revert synaptopathy of inner hair cells (IHCs) and behavioral signs of tinnitus in Mongolian gerbils following mild noise trauma. This experimental protocol led to minor hearing threshold shifts with no loss of auditory hair cells (HCs) but induced synaptopathy and a sustained and significant tinnitus percept. Treatment by intratympanic application of AC102 was evaluated in two protocols: 1. three weekly injections or 2. a single application. We evaluated hearing threshold changes using the auditory brainstem response (ABR) and the development of a tinnitus percept using the gap prepulse inhibition of acoustic startle (GPIAS) behavioral response. The number of IHC ribbon synapses along the cochlear frequency map were counted by immunostaining for the synaptic ribbon protein carboxy-terminal binding protein 2 (CTBP2). AC102 strongly and significantly reduced behavioral signs of tinnitus, as reflected by altered GPIAS. Noise-induced loss of IHC ribbon synapses was significantly reduced by AC102 compared to vehicle-treated ears. These results demonstrate that a single application of AC102 restores ribbon synapses following mild noise trauma thereby promoting recovery from tinnitus-related behavioral responses in vivo.

Authors with CRIS profile

Konstantin Tziridis Department of Otorhinolaryngology – Head and Neck Surgery (HNO-Klinik)

Involved external institutions

AudioCure Pharma GmbH DE Germany (DE) Wright Pharma Consult CH Switzerland (CH)

How to cite

APA:

Tziridis, K., Rasheed, J., Kwiatkowska, M., Wright, M., & Schlingensiepen, R. (2025). A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils. International Journal of Molecular Sciences, 26(11). https://doi.org/10.3390/ijms26115124

MLA:

Tziridis, Konstantin, et al. "A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils." International Journal of Molecular Sciences 26.11 (2025).

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