January 4, 2012 -- The December 2011 issue of the renowned scientific journal Otology & Neurotology presented new data on the otoprotective effects of AM-111, Auris Medical’s intracellular JNK ligand. In an article titled “Protection
Against Ischemic Cochlear Damage by Intratympanic Administration of AM-111” a research group around
Prof. Kiyofumi Gyo from the Department of Otolaryngology of Ehime University, Japan, showed the results
of a study with AM-111 in an animal model of transient cochlear ischemia. Vascular disturbances such as
an acute interruption of the blood supply to the cochlea are one of the factors that can trigger sudden sen-
sorineural hearing loss.
The Japanese scientists used a previously established model of transient cochlear ischemia for the study. In
this model the vertebral artery of gerbils is occluded for 15 minutes in order to provoke transient cochlear
ischemia, followed by reperfusion. As presented in earlier publications, this leads to irreversible loss espe-
cially of inner hair cells and permanent hearing loss especially at higher frequencies. 10 µl of AM-111 at a
concentration of 1, 10 or 100 µM and formulated in a gel was placed onto the round window membrane 30
minutes after the insult. The gel without active substance served as control. For the evaluation of the audi-
tory function, auditory brainstem responses (ABRs) were measured at 2, 4 and 8 kHz before ischemia, as
well as 4 days and 7 days after the temporary arterial occlusion. Animals were sacrificed on day 7 for histo-
pathology and counting of hair cells.
In control ears mean ABR thresholds increased substantially to day 4 (+31 dB at 8 kHz, the most sensitive
frequency) and from there recovered slightly to day 7 (+25 dB at 8 kHz). In contrast, ears treated with AM-
111 showed less hearing loss the higher the applied concentration was. At the highest concentration, mean
ABR thresholds in AM-111 protected ears rose by only 7 dB to day 4 and were elevated by 3 dB on day 7.
Statistical analysis (one-way analysis of variance followed by Fisher’s post hoc test) revealed statistical sig-
nificance of the otoprotective effect of AM-111 at all 3 concentrations (p < 0.01 at 100 and 10 µM, and p <
0.05 at 1 µM). The protective effect was confirmed by histopathology: inner hair cell loss on Day 7 in the
most affected basal turn amounted to 13.3±2.7% in controls and 3.1±0.6% in the highest concentration
AM-111 group. The difference was statistically significant in a concentration dependent fashion (p < 0.01 at
100 and 10 µM, and p < 0.05 at 1 µM).
About acute sensorineural hearing loss
Acute sensorineural hearing loss (ASNHL) or inner ear hearing loss is the consequence of various insults to
the cochlea. It may result e.g. from overexposure to noise, bacterial or viral infections, inflammation, vascu-
lar compromise, or a variety of other factors. In ASNHL, sensorineural structures of the inner ear – inner and
outer hair cells, neurons – are damaged, as well as other structures such as supporting cells or vascular
tissues. The common observation is a temporary increase in hearing thresholds, i.e. hearing loss. Thanks to
cellular defences and intrinsic repair mechanisms, a certain amount of such hearing loss is frequently recovered in the subsequent days and weeks. The remaining hearing loss however is irreversible. ASNHL may
be accompanied by other disorders of the inner ear such as dizziness or tinnitus.
When ASNHL develops into permanent hearing loss, it may have chronically debilitating consequences.
Hearing loss may have serious impacts on professional and personal lives, e.g. through avoidance or with-
drawal from social situations, reduced alertness and increased risk to personal safety, impaired memory and
ability to learn new tasks, or reduced job performance and earning power. Unfortunately, there exists no
standard therapy with proven efficacy for ASNHL so far.
AM-111 is a cell-permeable peptide that selectively blocks JNK MAPK mediated apoptosis of stress injured
hair cells and neurons in the cochlea. Major cochlear stress incidents that may result in irreversible hearing
loss include exposure to excessive noise, disturbances of the blood supply, viral or bacterial infections, and
exposure to certain ototoxic substances. When administered within a therapeutic window after the incident,
AM-111 can effectively protect cochlear hair cells and neurons that would otherwise undergo apoptosis
and be lost forever. AM-111’s otoprotective properties have been extensively tested and confirmed in vari-
ous animal models so far, including acute acoustic trauma, acute labyrinthitis, surgery trauma, aminoglyco-
side ototoxicity, semicircular canal injury in otitis media and cochlear ischemia. AM-111 has been granted
orphan drug status in both the European Union and the USA for the treatment of acute sensorineural hear-
ing loss. The active substance of AM-111 has been in-licensed by Auris Medical from Swiss biotechnology
company Xigen S.A.
About Auris Medical
Auris Medical is a Swiss biotechnology company developing specific pharmaceutical compounds for the
prevention or treatment of inner ear disorders, an area of great unmet medical need. Around the world,
many million people are suffering permanently from severe hearing loss and / or tinnitus, still lacking truly
effective and safe treatments for their disorders. Auris Medical is currently focusing on the development of
treatments for acute inner ear tinnitus (AM-101) and for acute sensorineural hearing loss (AM-111).
Dr. Thomas Meyer, Managing Director, telephone +41 61 201 13 50, firstname.lastname@example.org