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Hear Res. 2007 Apr;226(1-2):70-8. Epub 2006 Jul 12.

AM-111 protects against permanent hearing loss from impulse noise trauma.

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Naval Medical Center Spatial Orientation Center, 34800 Bob Wilson Dr. Suite 200, Naval Medical Center San Diego, San Diego, CA 92134-5000, USA.


The otoprotective peptide AM-111, a cell-permeable inhibitor of JNK mediated apoptosis, was tested for its efficacy as a rescue agent following impulse noise trauma. Single dose administrations of AM-111 at 1h or 4h post-impulse noise exposure (155 dB peak SPL) via systemic or local routes were evaluated with a total of 48 chinchillas. The animals received the compound either by IP injection or locally onto the round window membrane (hyaluronic acid gel formulation or osmotic mini-pump). Efficacy was determined by auditory brainstem responses (ABR) as well as cytocochleograms. Three weeks after impulse noise exposure, permanent threshold shifts (PTS) were significantly lower for AM-111 treated ears compared to controls, regardless of the drug administration route and the time point of drug delivery. Even the treatments which started 4h post-noise exposure, reduced hearing loss in the 2-8 kHz range compared to controls by up to 16-25 dB to a PTS as low as 6-17 dB, demonstrating significant protection against permanent hearing loss from impulse noise trauma. These findings suggest a key role for JNK mediated cochlear sensory cell death from oxidative stress.

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