Related Experiment Video
Updated: Nov 27, 2025
Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
Published on: February 10, 2023
BRAF inhibition protects against hearing loss in mice
Matthew A Ingersoll1, Emma A Malloy1, Lauryn E Caster1
1Department of Pharmacology and Neuroscience, School of Medicine, Creighton University, Omaha, NE 68178, USA.
Abstract:
Hearing loss caused by noise, aging, antibiotics, and chemotherapy affects 10% of the world population, yet there are no Food and Drug Administration (FDA)-approved drugs to prevent it. Here, we screened 162 small-molecule kinase-specific inhibitors for reduction of cisplatin toxicity in an inner ear cell line and identified dabrafenib (TAFINLAR), a BRAF kinase inhibitor FDA-approved for cancer treatment. Dabrafenib and six additional kinase inhibitors in the BRAF/MEK/ERK cellular pathway mitigated cisplatin-induced hair cell death in the cell line and mouse cochlear explants. In adult mice, oral delivery of dabrafenib repressed ERK phosphorylation in cochlear cells, and protected from cisplatin- and noise-induced hearing loss. Full protection was achieved in mice with co-treatment with oral AZD5438, a CDK2 kinase inhibitor. Our study explores a previously unidentified cellular pathway and molecular target BRAF kinase for otoprotection and may advance dabrafenib into clinics to benefit patients with cisplatin- and noise-induced ototoxicity.
Insights
Researchers identified dabrafenib, a BRAF kinase inhibitor, as a potential treatment to prevent hearing loss from chemotherapy and noise exposure. This discovery offers hope for new otoprotective therapies.
Area of Science:
- Ototolaryngology
- Pharmacology
- Cell Biology
Background:
- Hearing loss affects 10% of the global population, with limited FDA-approved preventative drugs.
- Current treatments do not address noise-induced or chemotherapy-induced ototoxicity.
Purpose of the Study:
- To screen kinase inhibitors for otoprotective properties against cisplatin toxicity.
- To identify novel molecular targets and pathways for preventing hearing loss.
Main Methods:
- Screened 162 small-molecule kinase inhibitors against cisplatin-induced inner ear cell toxicity.
- Utilized cell lines and mouse cochlear explants to assess hair cell death.
- Administered dabrafenib and AZD5438 orally to adult mice to evaluate otoprotection.
Main Results:
- Dabrafenib, a BRAF kinase inhibitor, significantly reduced cisplatin-induced hair cell death.
- Dabrafenib and other BRAF/MEK/ERK pathway inhibitors mitigated ototoxicity in vitro and in vivo.
- Oral dabrafenib repressed ERK phosphorylation and protected mice from cisplatin- and noise-induced hearing loss.
- Combination therapy with AZD5438 provided full protection against hearing loss in mice.
Conclusions:
- BRAF kinase is a novel molecular target for otoprotection.
- Dabrafenib shows promise for preventing cisplatin- and noise-induced ototoxicity.
- Further clinical investigation of dabrafenib for otoprotection is warranted.
