Given the exquisite delicacy of the hearing process, which entails transforming mechanical signals arising from vibrations in the air that enter our ears into electrical signals that can be perceived by our brains, it may seem fanciful to expect a mere drug to have any significant effect on hearing loss. Many of the therapeutic approaches that are currently in the clinic are nonspecific and are based simply on reducing oxidative damage arising from aging, exposure to excessive noise, certain cancer drugs and antibiotics, and other causes. The first drug targets being explored in the drug development programs now underway include ion channels and neurotransmitter receptors. “They're a little bit unimaginative,” says Ulrich Mueller, who chairs the department of molecular and cellular neuroscience at the Scripps Research Institute, in La Jolla, California. “On some level, I think we need new biology.”
Auris is not working with new biology as such, but it is the first to bring precisely targeted drugs to precisely defined patient populations. Its lead drug, an N-methyl-D-aspartate (NMDA) receptor antagonist called AM-101, will enter a phase 3 trial in tinnitus in Europe and the US later this year—it is seeking special protocol assistance from the US Food and Drug Administration at present. “We only enroll patients who can document the incident that triggered their tinnitus,” says CEO and founder Thomas Meyer. The company aims to eliminate those whose tinnitus resulted from injuries outside the cochlea, as it is delivering the drug to the cochlea by means of injection through the eardrum. The cochlea, a shell-like, fluid-filled chamber of the inner ear, is where the mechanical vibrations transmitted through the eardrum and across the three bones of the middle ear—the malleus, incus and stapes—are ultimately converted into electrical signals, which are then relayed to the brain through the auditory nerve. The key sensory transduction step occurs in the inner hair cells of the cochlea, which generate an action potential in response to relative movement between the cells' stereocilia and the surrounding cochlear fluid.
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