AM-111 reduces hearing loss in a guinea pig model of acute labyrinthitis.
OBJECTIVE
This study investigated the otoprotective properties of AM-111, an inhibitor of c-Jun N-terminal kinase-mediated apoptosis and inflammation.


METHODS
A controlled, prospective animal study using a guinea pig model of acute labyrinthitis.


METHODS
Acute labyrinthitis was generated by injection of antigen into the scala tympani of sensitized guinea pigs. Treatment groups received 100 microL of AM-111 at concentrations of 100 micromol/L, 10 micromol/L, and 1 micromol/L in a hyaluronic acid gel formulation delivered over the round window niche within 1 hour of antigen challenge. Cochlear function was monitored over 21 days with serial auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) measurements followed by histologic analysis.


RESULTS
The ABR results on day 21 demonstrated that untreated control ears for acute labyrinthitis had a mean hearing loss (HL) of 68 +/- 12 dB. In contrast, ears treated with AM-111 (100 micromol/L) had a mean HL of 39 +/- 31 dB. These two groups were statistically different (one-way analysis of variance, P = .03). Secondary outcomes, including DPOAE shift, inner hair cell survival, inflammatory cell counts, and spiral ganglion density, were also statistically significant in favor of an otoprotective effect of AM-111. Lower doses of AM-111 did not produce a statistically significant reduction in HL over controls.


CONCLUSIONS
AM-111 delivered over the round window membrane in a 100 microL hyaluronic acid formulation at a 100 micromol/L concentration immediately after induction of acute labyrinthitis in the guinea pig cochlea protects hearing, reduces hair cell loss, and reduces the number of inflammatory cells at 21 days after treatment.
Barkdull
Gregory C
GC
Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California San Diego, San Diego, CA 92103-8895, USA. gbarkdul@ucsd.edu
Hondarrague
Yannick
Y
Meyer
Thomas
T
Harris
Jeffrey P
JP
Keithley
Elizabeth M
EM
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D005500:Follow-Up Studies; D006168:Guinea Pigs; D034381:Hearing Loss / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007762:Labyrinthitis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010455:Peptides / Q000627:therapeutic use*; D011446:Prospective Studies; D013136:Spiral Ganglion / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D010455:Peptides; C478085:D-JNKI-1