ArticleCell death & disease2024
A preoperative dose of the pyridoindole AC102 improves the recovery of residual hearing in a gerbil animal model of cochlear implantation.
Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Assessment of Safety, Tolerability, Pharmacokinetics, and Volume-Dependent Conductive Hearing Loss in Healthy Volunteers: First-in-Human, Open-Label, Placebo-Controlled Study of a Single Intratympanic Injection of AC102.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2025Trial
- Subtype-Specific Vulnerability of Spiral Ganglion Neurons in Sensorineural Hearing Loss Across the Lifespan.Brain sciences · 2026Review
- Visualization of the Spiral Ganglion Neuron in Vivo Using a NovelAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils.International journal of molecular sciences · 2025Article
- SIRT1 prevents noise-induced hearing loss by enhancing cochlear mitochondrial function.Cell communication and signaling : CCS · 2025Article
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14 authors.
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Abstract
Sensorineural hearing loss (SNHL) is the most common sensory deficit worldwide. Due to the heterogeneity of causes for SNHL, effective treatment options remain scarce, creating an unmet need for novel drugs in the field of otology. Cochlear implantation (CI) currently is the only established method to restore hearing function in profound SNHL and deaf patients. The cochlear implant bypasses the non-functioning sensory hair cells (HCs) and electrically stimulates the neurons of the cochlear nerve. CI also benefits patients with residual hearing by combined electrical and auditory stimulation. However, the insertion of an electrode array into the cochlea induces an inflammatory response, characterized by the expression of pro-inflammatory cytokines, upregulation of reactive oxygen species, and apoptosis and necrosis of HCs, putting residual hearing at risk. Here, we characterize the small molecule AC102, a pyridoindole, for its protective effects on residual hearing in CI. In a gerbil animal model of CI, AC102 significantly improves the recovery of hearing thresholds across multiple frequencies and confines the cochlear trauma to the directly mechanically injured area. In addition, AC102 significantly preserves auditory nerve fibers and inner HC synapses throughout the whole cochlea. In vitro experiments in an ethanol challenged HT22 cell-line revealed significant and dose-responsive anti-apoptotic effects following the treatment of with AC102. Further, AC102 treatment resulted in significant downregulation of the expression of pro-inflammatory cytokines in an organotypic ex vivo model of electrode insertion trauma (EIT). These results suggest that AC102's effects are likely elicited during the inflammatory phase of EIT and mediated by anti-apoptotic and anti-inflammatory properties, highlighting AC102 as a promising compound for hearing preservation during CI. Moreover, since the inflammatory response in CI shares similarities to that in other etiologies of SNHL, AC102 may be inferred as a potential general treatment option for various inner ear conditions.
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