ERLANGEN & BERLIN, GERMANY — The novel compound AC102 almost completely reversed tinnitus in a preclinical model after a single dose. At the same time, the damaged connections between the auditory nerve and inner ear sensory cells were restored. These findings were recently published in the International Journal of Molecular Sciences in a joint study conducted by Erlangen University Hospital and Berlin-based drug developer AudioCure.
With no currently available drug treatments for tinnitus, the medical need remains high.
Significant Improvement Observed After Acoustic Trauma
In the study, AC102 was administered to the middle ear of one experimental group after acoustic trauma, while a second group received a placebo. Although both groups initially exhibited signs of tinnitus, symptoms in the AC102 group had nearly disappeared after five weeks—marking a clear contrast to the placebo group.
Additionally, the AC102 group demonstrated significantly less loss of synaptic connections between the inner ear and the auditory nerve. This synaptic damage is widely considered a potential cause of tinnitus.
“Our results suggest regeneration of inner ear structures that are critical for tinnitus and could be an important milestone and a glimmer of hope for a causal treatment of tinnitus,” said Dr. Konstantin Tziridis, first author of the study and researcher at Erlangen University Hospital.
A Closer Look at the Mechanisms and Methods
The researchers used an established animal model to induce tinnitus via acoustic trauma. Behavioral evidence of tinnitus was assessed using the gap prepulse inhibition of the acoustic startle response (GPIAS), a widely accepted method for detecting the presence of tinnitus in rodents.
AC102 was delivered transtympanically—into the middle ear—24 hours after the trauma.
According to the researchers, AC102 treatment not only led to the disappearance of tinnitus-like behavior in the animal model but also supported synaptic repair between inner hair cells and spiral ganglion neurons. Histological analysis revealed significant preservation and even regeneration of ribbon synapses, a finding that supports the hypothesis of synaptopathy as a key mechanism underlying tinnitus and hidden hearing loss.
Notably, hearing thresholds measured via auditory brainstem responses (ABRs) were not significantly improved by AC102 in this study, suggesting that the compound’s therapeutic benefit lies specifically in treating neural deficits rather than restoring pure tone thresholds. The researchers point out that this could represent a novel mode of action for tinnitus therapy, distinct from interventions aimed solely at cochlear hair cell function.
A Potential Therapeutic Option for Hearing Loss and Tinnitus
Tinnitus affects approximately 10–15% of adults, and up to two-thirds of sudden hearing loss patients also experience tinnitus, with persistent symptoms in around 30% of cases. Despite the high prevalence, there is still no effective causal treatment.
AC102 is being investigated as a potential solution. In a preclinical acoustic trauma model, the compound not only reversed sudden hearing loss but also demonstrated the ability to reduce tinnitus symptoms. Given the frequent overlap of these conditions, AudioCure is evaluating AC102’s dual potential in an ongoing clinical study.
“Constant ear noise caused by tinnitus can be even more stressful for many patients than the hearing loss itself. With AC102, we hope to eventually have an effective remedy for both conditions. This would be a great relief for patients and doctors who have no approved drug treatment available at present.”
–Dr. Reimar Schlingensiepen, CEO of AudioCure
AC102 has already undergone safety and tolerability evaluation in a clinical study and is currently being tested in a Europe-wide Phase 2 trial to assess its efficacy in treating sudden hearing loss and tinnitus.
If these results can be replicated in humans, AC102 may offer a much-needed breakthrough for patients affected by these common yet undertreated auditory conditions.
Citation:
Tziridis, K., Oestreicher, N., Braun, S., Vengel, N., Krauss, P., Krinner, S., Rau, A., Luber, M., Wrzosek, G., & Schulze, H. (2023). Treatment of Synaptopathy-Related Hearing Loss and Tinnitus with Transtympanic Delivery of AC102 in a Preclinical Mouse Model. International Journal of Molecular Sciences, 26(15), 5124. https://doi.org/10.3390/ijms26155124
