Animal studies underscore the effectiveness of AUT00063. In an abstract presented in 2014 at the Midwinter Meeting of the Association for Research in Otolaryngology in San Diego, an Autifony-sponsored study showed that the drug significantly improved auditory temporal processing in a rat model of ARHL. The results suggest that AUT00063, “via positive modulation of Kv3 channels, has potential in the treatment of age-related hearing impairment,” the investigators concluded.
Explore This IssueJune 2015
QUIET-1 Tinnitus Trial
Hearing loss isn’t the only focus of Autifony; the company also is conducting a trial of AUT00063 in patients with tinnitus, known as QUIET-1. The U.K.-based study began in October 2014, according to Dr. Domayne-Hayman, and seeks to improve tinnitus in patients who have experienced symptoms for at least six months, but no more than 18 months, from diagnosis. That is the point in time, she noted, when the condition has shifted from one caused by localized damage to hair cells in the inner ear to a more centralized problem mediated by the central nervous system and brain.
“In the beginning of our research with AUT00063, we only focused on ARHL,” she said. “But given the overlap we were seeing in how important the brain is to both hearing loss and tinnitus and the strong preclinical data we got in tinnitus models, we realized there was an opportunity to study both conditions and potentially have a huge societal impact, given how prevalent they are in our aging population.”
A Focus on Acute Disease
While Autifony continues its focus on patients whose tinnitus has shifted to a chronic, centralized pattern of symptoms, Dr. Meyer and his research team at Auris Medical are focused on the acute stage of the hearing disorder, before it becomes centralized and is no longer amenable to treatment.
Their weapon of choice is AM-101, a drug that targets N-methyl-D-aspartate (NMDA) activity. NMDA receptors, he explained, are located at the post-synapse of inner hair cells and become activated after traumatic injury (Ann N Y Acad Sci. 1999;884:249-254). In some cases, acute hearing loss and tinnitus resolve spontaneously after such injury. In other instances, however, NMDA receptors remain pathologically active and generate the phantom “noise” that typifies tinnitus, Dr. Meyer said.
AM-101 has been shown to be safe and effective in two phase 2 trials. In one of the studies, patients treated with AM-101 reported experiencing significant reductions in tinnitus loudness, annoyance, and tinnitus-related sleep difficulties when compared with the placebo (Otol Neurotol. 2014;35:589-597). The benefits were dose dependent and increased gradually during the 90 days of observation.