AM-111 protects against hearing loss from cochlear implant electrode insertion trauma

March 2011

New research data presented at the recent Midwinter Meeting of the Association for Research in Otolaryn-gology (ARO) provided further evidence of AM-111's otoprotective effects, Auris Medical's novel intracellu-lar drug for the treatment of inner ear disorders. A single dose of AM-111 administered in a gel formulation onto the round window membrane of guinea pigs 30 minutes prior to the insertion of a cochlear implant electrode led to a persistent and statistically highly significant recovery of hearing thresholds following the procedure. The recovery was measured by auditory brainstem responses to 0.5 and 16 kHz pure tone stimuli.

Cochlear implantation allows certain deaf or hard of hearing patients to regain hearing through direct elec-trical stimulation of the auditory nerve. As the implantation is an invasive procedure, parts of the cochlea may be damaged mechanically or through various other effects such as oxidative stress and inflammation. While these effects are of less importance in case of patients who were already profoundly deaf prior to implantation, protection from insertion trauma is important whenever residual hearing shall be preserved. Novel approaches seek e.g. to use electric acoustic stimulation (a combination of cochlear implant for high frequencies and hearing aid for low frequencies). Hearing preservation could thus provide important clinical benefits in such cases.

The new data were presented by a US research team led by Adrien Eshraghi, MD, Director of the University of Miami Hearing Research Laboratory. Earlier work by this research group had already shown that AM-111 delivered by direct perfusion for several days into the cochlea protected against permanent hearing loss from cochlear implant electrode insertion trauma. Their new study used not only a more sophisticated ani-mal model, but also a much more practical and clinically relevant method of delivery for the administration of AM-111. The results of the study, which was supported by grants from Med-El and Auris Medical, shall be published in a scientific journal.

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 re-covered 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.

About AM-111

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).