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Updated: Aug 17, 2026
Neuro-rehabilitation Approach for Sudden Sensorineural Hearing Loss
Published on: January 25, 2016
Prevention of noise-induced hearing loss with Src-PTK inhibitors
Kelly Carney Harris1, Bohua Hu, David Hangauer
1Center for Hearing and Deafness, University at Buffalo, Buffalo, NY 14214, USA. harriskc@musc.edu
Abstract:
Studies from our lab show that noise exposure initiates cell death by multiple pathways [Nicotera, T.M., Hu, B.H., Henderson, D., 2003. The caspase pathway in noise-induced apoptosis of the chinchilla cochlea. J. Assoc. Res. Otolaryngol. 4, 466-477] therefore, protection against noise may be most effective with a multifaceted approach. The Src protein tyrosine kinase (PTK) signaling cascade may be involved in both metabolic and mechanically induced initiation of apoptosis in sensory cells of the cochlea. The current study compares three Src-PTK inhibitors, KX1-004, KX1-005 and KX1-174 as potential protective drugs for NIHL. Chinchillas were used as subjects. A 30 microl drop of one of the Src inhibitors was placed on the round window membrane of the anesthetized chinchilla; the vehicle (DMSO and buffered saline) alone was placed on the other ear. After the drug application, the middle ear was sutured and the subjects were exposed to noise. Hearing was measured before and several times after the noise exposure and treatment using evoked responses. At 20 days post-exposure, the animals were anesthetized their cochleae extracted and cochleograms were constructed. All three Src inhibitors provided protection from a 4 h, 4 kHz octave band noise at 106 dB. The most effective drug, KX1-004 was further evaluated by repeating the exposure with different doses, as well as, substituting an impulse noise exposure. For all conditions, the results suggest a role for Src-PTK activation in noise-induced hearing loss (NIHL), and that therapeutic intervention with a Src-PTK inhibitor may offer a novel approach in the treatment of NIHL.
Insights
Three Src-PTK inhibitors protected against noise-induced hearing loss (NIHL) in chinchillas. KX1-004 demonstrated the most significant protective effects, suggesting Src-PTK inhibitors as a novel therapeutic approach for NIHL.
Area of Science:
- Oto-science
- Cellular Biology
- Pharmacology
Background:
- Noise exposure triggers cell death via multiple pathways, necessitating multifaceted protection strategies.
- The Src protein tyrosine kinase (PTK) signaling cascade is implicated in apoptosis initiation within cochlear sensory cells due to metabolic or mechanical stress.
Purpose of the Study:
- To evaluate the efficacy of three Src-PTK inhibitors (KX1-004, KX1-005, KX1-174) as potential therapeutic agents for preventing noise-induced hearing loss (NIHL).
Main Methods:
- Chinchillas were treated with Src inhibitors or vehicle applied to the round window membrane.
- Subjects were exposed to octave band noise, and hearing was monitored using evoked responses.
- Cochleograms were constructed 20 days post-exposure to assess structural damage.
Main Results:
- All three Src inhibitors provided significant protection against a 4-hour, 4 kHz octave band noise exposure at 106 dB.
- KX1-004 exhibited the most potent protective effects and was further validated with varying doses and impulse noise exposure.
- Results consistently indicated a role for Src-PTK activation in NIHL.
Conclusions:
- Src-PTK activation is involved in the pathogenesis of noise-induced hearing loss.
- Therapeutic intervention using Src-PTK inhibitors presents a promising novel strategy for treating and preventing NIHL.
