ArticleProceedings of the National Academy of Sciences of the United States of America2024
A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- 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
- Review
- Rational Design of Inner Ear Drug Delivery Systems.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- A Single Dose of AC102 Reverts Tinnitus by Restoring Ribbon Synapses in Noise-Exposed Mongolian Gerbils.International journal of molecular sciences · 2025Article
- Noise-Induced Hearing Loss: Overview and Future Prospects for Research on Oxidative Stress.International journal of molecular sciences · 2025Review
- Current Role of the Nonsteroid Treatment of Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL): A Narrative Review.Journal of clinical medicine · 2025Review
- Clinical trials in otology and neurotology: state of the science.Frontiers in neurology · 2025Review
- SOD mediates mitochondrial epigenetic regulation in NIHL.Frontiers in cellular neuroscience · 2025Article
- A preoperative dose of the pyridoindole AC102 improves the recovery of residual hearing in a gerbil animal model of cochlear implantation.Cell death & disease · 2024Article
- Drug selection for inner ear therapy.Frontiers in pharmacology · 2024Article
- Article
- Impact of Hospital Ward Acoustic Design on Postoperative Recovery of Patients with Acute Myocardial Infarction.Noise & healthArticle
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although sudden sensorineural hearing loss (SSNHL) is a serious condition, there are currently no approved drugs for its treatment. Nevertheless, there is a growing understanding that the cochlear pathologies that underlie SSNHL include apoptotic death of sensory outer hair cells (OHCs) as well as loss of ribbon synapses connecting sensory inner hair cells (IHCs) and neurites of the auditory nerve, designated synaptopathy. Noise-induced hearing loss (NIHL) is a common subtype of SSNHL and is widely used to model hearing loss preclinically. Here, we demonstrate that a single interventive application of a small pyridoindole molecule (AC102) into the middle ear restored auditory function almost to prenoise levels in a guinea pig model of NIHL. AC102 prevented noise-triggered loss of OHCs and reduced IHC synaptopathy suggesting a role of AC102 in reconnecting auditory neurons to their sensory target cells. Notably, AC102 exerted its therapeutic properties over a wide frequency range. Such strong improvements in hearing have not previously been demonstrated for other therapeutic agents. In vitro experiments of a neuronal damage model revealed that AC102 protected cells from apoptosis and promoted neurite growth. These effects may be explained by increased production of adenosine triphosphate, indicating improved mitochondrial function, and reduced levels of reactive-oxygen species which prevents the apoptotic processes responsible for OHC death. This action profile of AC102 might be causal for the observed hearing recovery in in vivo models.
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