Editor: Here’s the latest information on the otoprotective effects of AM-111. This release also mentions their work on tinnitus medication (AM-101).
February 19, 2007
New research data suggesting otoprotective effect of AM-111 also in acute Labyrinthitis
New research data presented at the Midwinter Research Meeting of the Association for Research in Otolaryngology (ARO) in Denver (Colorado, USA) provided further evidence for the otoprotective effect of AM-111, Auris Medical’s cell-permeable JNK inhibitor for the treatment of acute sensorineural hearing loss. A poster presented by the University of California at San Diego (UCSD), Veterans Medical Research Foundation and Auris Medical showed some first results obtained with AM-111 in an animal model of acute labyrinthitis.
For the study, sterile labyrinthitis was induced in guinea pigs through systemic sensitization with keyhole limpet hemocyanide (KLH), followed later by intracochlear KLH administration. This resulted in a vigorous inflammatory response and significant sensorineural hearing loss (> 70 dB after three days). AM-111 was delivered in a 100 µL gel formulation onto the round window membrane at a concentration of 100 µM immediately after intracochlear KLH administration. Compared to untreated control animals with acute labyrinthitis, AM-111 treated animals showed a less severe course of hearing loss as early as on day 3, with the protective effect improving further until the end of the observation period on day 21 (p < 0.04, twotailed paired student’s t-test). In addition, the histopathological examination revealed a lower loss of inner and outer hair cells as well as a lower number of inflammatory cells in the cochlea.
The otoprotective effect of the JNK inhibitor AM-111 in acute labyrinthitis may be the result of blocking apoptotic pathways triggered by pro-inflammatory cytokines such as TNF-_ or IL-1ß. JNK is known to regulate expression of genes involved in inflammation and apoptosis. Further studies are planned with AM- 111 to explore the therapeutic potential of the compound as well as to elucidate its mechanism of action in acute labyrinthitis.
About acute labyrinthitis
The fluid-filled canals that make up the inner ear are called the labyrinth. Acute labyrinthitis is an inflammation of these tissues with symptoms that may include hearing loss, dizziness, loss of balance, tinnitus or involuntary eye movements. Acute labyrinthitis may be linked to a bacterial or viral infection.
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 various animal models so far, including acute acoustic trauma, surgery induced acoustic trauma (cochlear implant electrode insertion) and aminoglycoside ototoxicity. AM-111 has been granted orphan drug status in both the European Union and the USA for the treatment of acute sensorineural hearing 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-French biotechnology company developing specific medicinal products 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 inner ear tinnitus (AM-101) and for acute sensorineural hearing loss (AM-111).