Chemistry:AUT-00063
AUT00063 (also called AUT-00063) is an investigational small-molecule compound developed by Autifony Therapeutics for hearing loss and tinnitus.[1]
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.[2]
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.[3]
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.[4]
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.".[4]
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.[5]
See also
References
- ↑ "Autifony Therapeutics Initiates Phase I Study of Hearing Loss and Tinnitus Medication". 2013-06-05. https://hearingreview.com/hearing-loss/tinnitus/autifony-therapeutics-initiates-phase-i-study-hearing-loss-and-tinnitus-medication.
- ↑ "Pharmacological modulation of Kv3.1 mitigates auditory midbrain temporal processing deficits following auditory nerve damage". Scientific Reports 7 (1). 2017. doi:10.1038/s41598-017-17406-x. PMID 29235497. Bibcode: 2017NatSR...717496C.
- ↑ "Autifony Therapeutics awarded £2.2 million to progress first-in-class drug for tinnitus into Phase IIa study". Autifony Therapeutics Ltd.. 2014-06-04. https://autifony.com/wp-content/uploads/2022/05/Autifony-TSB-tinnitus-Ph1-FINAL-4-Jun-2014.pdf.
- ↑ 4.0 4.1 "A balanced randomised placebo controlled blinded phase IIa multi-centre study to investigate the efficacy and safety of AUT00063 versus placebo in subjective tinnitus: The QUIET-1 trial". Hearing Research 377: 153–166. June 2019. doi:10.1016/j.heares.2019.03.018. PMID 30939361.
- ↑ "Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus". Hearing Research 361: 36–44. April 2018. doi:10.1016/j.heares.2018.01.017. PMID 29453003.
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