student research day - Case Western Reserve University School of ...

Jonathan Frankel & Alex Levitt
Testing of Therapeutic Agent to Prevent Hearing Loss in Animal Model of
Endolymphatic Hydrops
Jonathan Frankel,* Alex Levitt* and Chris Heddon,* Sami Melki *
*These authors made equal contributions and should be considered co-first authors.
Kumar Alagramam, Cliff Megerian
Department of Otolaryngology Head and Neck Surgery
University Hospitals Case Medical Center, Case Western Reserve University, Cleveland, Ohio 44106
Meniere’s Disease (MD) is associated with tinnitus, episodic vertigo, endolyphatic hydrops (ELH) and hearing loss,
and MD affects ~1 in 5,000 each year. No treatment is available to delay or prevent hearing loss linked to MD.
Although the etiology of MD is unknown, glutamate induced excitotoxicity of cochlear neuronal cells is well
established.
We hypothesize that glutamate release blockers will prevent permanent hearing loss linked to MD.
The pharmaceutical agent Riluzole, a known glutamate release blocker, was administered intraperitoneally daily
to BALB/c-Phex mutant mice, a model for ELH-associated hearing loss. Preservation of hearing function in
treated mice was quantified based on auditory-evoked brainstem response (ABR) at postnatal day 21 (P21), P25,
and P30. Time points were chosen based on previous work showing ABRs for BALB/c-Phex mice reliably
measured after P21 with definitive hearing loss occurring at P30.
Preliminary results show that the average hearing loss in untreated mutants is greater than mutants treated with
Riluzole; this difference was far greater at P21 compared to P25 or P30. Further experiments are underway to
confirm these results.
These results corroborate the role of glutamate excitotoxicity in the pathogenesis of Meniere’s disease and
demonstrate that the progression of hearing loss can be retarded by Riluzole, a drug that inhibits glutamate
release.
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