August 31, 2010 –The otoprotective effects of AM-111, Auris Medical’s novel intracellular drug for the treatment of inner ear disorders, have been further confirmed by promising new data presented at the Inner Ear Biology Workshop 2010 in Prague (Czech Republic). A research group led by Prof. Kiyofumi Gyo (Ehime University, Japan), showed in a poster presentation the results of a study with AM-111 in an animal model of transient co- chlear ischemia. Vascular disturbances such as an acute interruption of the blood supply to the cochlea are one of the factors that can trigger sudden sensorineural 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 temporarily occluded in order to provoke transient cochlear ischemia. As previously shown, this leads to loss of inner hair cells and permanent hearing loss. 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 15 minutes after ischemia. The gel without active substance served as control. For the evaluation of the auditory 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 histopathology and counting of inner hair cells.
The study showed a concentration dependent otoprotective effect of AM-111 in transient cochlear ische- mia. While 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 (+24 dB at 8 kHz), ears treated with AM-111 showed less hearing loss the higher the concentration. At the highest dose (100 µM), 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, which is a signifi- cantly different from control values. The protective effect was confirmed by histopathology, which also showed a concentration dependent reduction in mean inner hair cell loss that was statistically significant at the highest doses.
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).
Contact:
Dr. Thomas Meyer, Managing Director, telephone +41 61 201 13 50, tm@aurismedical.com
