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

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.

• Authors: John K M Coleman, Cherllynn Littlesunday, Ronald Jackson, Thomas Meyer
• Journal: Hearing research (Hear Res) Vol. 226 Issue 1-2 Pg. 70-8 (Apr 2007) ISSN: 0378-5955 [Print] Netherlands
• PMID: 16839720 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

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

Topics

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