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

Hear Res. 2007 Apr;226(1-2):70-8. doi: 10.1016/j.heares.2006.05.006. Epub 2006 Jul 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Chinchilla
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Female
  • Gels
  • Hair Cells, Auditory / drug effects
  • Hair Cells, Auditory / pathology
  • Hearing Loss, Noise-Induced / enzymology
  • Hearing Loss, Noise-Induced / pathology
  • Hearing Loss, Noise-Induced / physiopathology
  • Hearing Loss, Noise-Induced / prevention & control*
  • Infusion Pumps, Implantable
  • Injections, Intraperitoneal
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Peptides / administration & dosage
  • Peptides / pharmacology*

Substances

  • Enzyme Inhibitors
  • Gels
  • Peptides
  • JNK Mitogen-Activated Protein Kinases