CATEGORY:
Research
SCREENSHOT:
TITLE:
A single dose of AC102 restores hearing in a guinea pig model of noise-induced hearing loss to almost prenoise levels
CONTENT:
Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2314763121. doi: 10.1073/pnas.2314763121. Epub 2024 Apr 1.
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.
PMID:38557194 | DOI:10.1073/pnas.2314763121
SOURCE:
Proceedings of the National Academy of Sciences of the United States of America
PUBLISHER:
PMID:
pubmed:38557194
ID:
0b58ea4968e09ff10f4e1238c494f316pubmed:38557194
DOI:
10.1073/pnas.2314763121
DATE – PUBLISHED:
Mon, 01 Apr 2024 06:00:00 -0400
DATE – DOI:
2024-04-01T19:06:53Z
DATE – ADDED:
04/01/24 06:38PM
LINK – PUBMED:
https://pubmed.ncbi.nlm.nih.gov/38557194/
LINK – DOI:
https://doi.org/10.1073/pnas.2314763121
LINK – PUBLISHER:
https://pnas.org/doi/10.1073/pnas.2314763121?utm_source=hearinglosstreatmentreport.com
IMAGE:
REFERENCE:
Hearing Loss Treatment Report, Urgent Research, 2024-04-01T22:38:34+00:00, https://www.hearinglosstreatmentreport.com.