Hearing disorders and hearing loss: Autifony Therapeutics has a new approach to treating hearing disorders and is now recruiting for clinical trials

Autifony Science

Hearing Disorders

Autifony’s approach to hearing disorders and hearing loss is to target particular ion channels, known as Kv3 voltage gated potassium channels, which play a key role at many levels of the central auditory pathway. Studies conducted by Prof Len Kaczmarek’s group at Yale University suggest that Autifony’s Kv3 modulators may help to restore the timing of firing of neurons in the auditory brainstem important for central auditory processing.

For Age Related Hearing Loss

In age-related hearing loss, there is evidence for an age-related decline in expression of Kv3 channels. The reduction of these channels and the corresponding loss of function of certain auditory neurons may contribute to the reduction in hearing acuity and difficulty that patients experience in understanding speech. Autifony’s drug is designed to modulate Kv3 channels, improve hearing acuity, and thus reduce some of the symptoms of age-related hearing loss, in particular difficulty with speech understanding. Studies in preclinical models conducted by Autifony’s academic collaborators at the Institute of Experimental Medicine in Prague (led by Prof Josef Syka) show that Autifony’s drugs can improve key aspects of hearing acuity in aged animals. A Phase IIa age related hearing loss clinical trial is now underway in the US to test this in humans.

For Tinnitus

Tinnitus is characterised by a range of empirical observations, several hypotheses exist to explain how altered central auditory processing leads to the emergence of phantom sounds. Studies to date confirm the importance of Kv3 channels at all levels of the auditory pathway. Profiling of our lead compound shows it can modulate function in both brainstem and cortex in ways that could be beneficial in the treatment of tinnitus. Our research with academic collaborators at UCL’s Ear Institute (led by Dr Jennifer Linden) and at the University of Southern Illinois (led by Dr Jeremy Turner) shows that Autifony’s drugs can reduce both the behavioural and electrophysiological correlates of tinnitus in preclinical models. A Phase IIa tinnitus clinical trial is now underway in the UK to test this in humans.

For Noise Induced Hearing Loss

Acute or chronic noise can damage the cochlea, initiating a series of adaptive as well as maladaptive changes within central auditory pathways that contribute to the perceived hearing loss and sometimes the emergence of tinnitus. In collaborative studies with the University of Leicester (led by Dr Martine Hamann) we have shown that one of the changes in the central nervous system following noise is the reduced function of Kv3 channels in the auditory brainstem (Pilati et al. 2012, Hearing Research 283:98-106). Further studies in preclinical models with the University of Southern Illinois (led by Prof Kathy Campbell) suggest that Autifony’s drugs can protect against hearing loss induced by loud noise.

For Cochlear Implant Users:

Cochlear implants have transformed the lives of people with profound hearing loss, but not all outcomes are optimal and there are many adult CI users who still struggle to understand speech, particularly in noisy environments. Fundamental to the ability to decode speech, especially in a noisy background, is the ability to detect the rapid sounds that make up speech.  Hearing loss and ageing are associated with deterioration of the neural circuits that underpin central auditory processing, which leads to a reduction in auditory temporal resolution. Autifony’s drug modulates voltage-gated Kv3 potassium channels, which are critical to the function of neural circuits involved in central auditory processing. It is thought that by increasing the precision and timing of neural firing, AUT00063 will enhance people’s hearing performance with their cochlear implant. ​

Please see Scientific Publications page for further information on Autifony’s scientific approach.​

Schizophrenia​

Given Autifony’s focus on modulation of Kv3 channels, which have also been implicated in other neurological and psychiatric disorders, there are opportunities for Autifony to investigate these other indications with compounds with different profiles.

We have identified Kv3 potassium channels as new targets for the treatment of schizophrenia.Their importance lies in their role in the control of parvalbumin-positive (PV+) interneurons that are thought to be dysfunctional in schizophrenia (Lewis et al, 2012, Cortical parvalbumin interneurons and cognitive dysfunction in schizophrenia. Trends in Neurosciences, 35(1), 57-67).  We propose that positive modulation of Kv3 channels will enhance PV+ interneuron function and thus reduce positive, negative, and cognitive symptoms of schizophrenia.

In 2013, Autifony was awarded Innovate UK (previously known as Technology Strategy Board) funding to progress over the next two years the development of a candidate drug for the treatment of schizophrenia.  Autifony are working with academic collaborators in Manchester and Newcastle Universities to obtain a greater understanding of the role of Kv3 channels in schizophrenia and to explore the potential benefit of Kv3 modulators in the treatment of this serious psychiatric disorder.​ In 2015, Autifony was awarded further funding from Innovate UK to continue this successful preclinical collaboration and to take the programme into clinical trials, in collaboration with the University of Manchester and the Institute of Psychiatry, Psychology & Neuroscience, Kings College London.

Please see Scientific Publications page for further information on Autifony’s scientific approach.