AUT00063 (also called AUT-00063) is an investigational small-molecule compound developed by Autifony Therapeutics for hearing loss and tinnitus.
Background and development AUT00063 was identified as a modulator of Kv3 (Shaw) family potassium channels, which play a role in the firing properties of auditory neurons and are implicated in central auditory hyper-activity hypotheses of tinnitus. In June 2014 Autifony announced that it had been awarded a £2.2 million grant from the UK's Technology Strategy Board (now Innovate UK) toward a Phase IIa clinical trial in tinnitus patients.
Clinical trials
Tinnitus (QUIET-1) A randomised, double-blind, placebo-controlled Phase IIa study (EudraCT 2014–002179–27) titled "QUIET-1" enrolled participants with subjective tinnitus to assess efficacy and safety of AUT00063 versus placebo. However, the trial was terminated early for futility: Autifony announced on 28 April 2016 that headline data from QUIET-1 "confirm lack of efficacy of AUT00063 in the treatment of people with mild-to-moderate tinnitus.".
Mechanism of action AUT00063 targets Kv3 (Shaw) potassium channels, which are voltage-gated channels expressed in the central auditory pathway and help control rapid repolarization and high-frequency firing of neurons. By modulating these channels, the drug aimed to reduce abnormal spontaneous activity (a proposed substrate of tinnitus) in central auditory circuits.
See also List of investigational tinnitus drugs
References