A recently published special issue of International Journal of Molecular Science reviewed a variety of therapeutic interventions currently being studied as novel strategies to restore hearing.
One of these strategies involves the use of “KCNQ4 activators” as a way to keep the inner ear functioning properly. And according to the paper, existing drugs (or combinations thereof) that are already approved could potentially be repurposed as therapies for sensorineural hearing loss.
From the May 26, 2021 paper titled, “Molecular Mechanisms of Sensorineural Hearing Loss and Development of Inner Ear Therapeutics”:
The voltage-gated potassium channel KCNQ4 has an essential role in regulating auditory function in the inner ear, by contributing to potassium recycling and maintenance of cochlear homeostasis. Reduced activity of the KCNQ4 channel has been associated with a genetic form of hearing loss, noise-induced hearing loss, and age-related hearing loss. Rim and colleagues presented a comprehensive review of 90 publications looking at the KCNQ4 as a potential therapeutic target for the treatment of hearing loss. In this review, the authors updated the current concepts of the physiological and pathophysiological roles of KCNQ4 in the inner ear and focused on the role of KCNQ4 activators in therapeutic management of different forms of hearing loss. They propose that the simultaneous application of two activators with distinct modes of action may result in synergistic effects and reduced off-target effects. It was also suggested that drug repurposing may be an attractive option for clinical development of KCNQ4 activators as therapies for hearing loss.
Another recent paper, from three months ago (published March 2, 2021) titled, “Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss”, stated:
Therefore, the discovery of small compounds activating or potentiating KCNQ4 is an important strategy for the curative treatment of hearing loss.
The authors concluded by recommending that “KCNQ4 activators should be validated in clinical trials, as there is no ongoing clinical trial targeting hearing loss by KCNQ4 activators currently.”
But do not let the fact that KCNQ4 activators have not yet entered human clinical trials mislead you. Despite the current lack of trials, that does not automatically mean these drugs are far, far away.
Because, as the authors also pointed out earlier in the same paper: “Drug repurposing and optimization for applicable specific KCNQ4 mutation might also be an option for clinical application of KCNQ4 activators […] with advantages of reducing the cost and shortening the time when compared to de novo drug discovery.”
As far as what to keep an eye out for next, on the topic of KCNQ4, the researchers also tip us off as to which company is working on this mechanism most closely:
Acousia Therapeutics, which is a biotech company aiming for the development of small-molecule drugs for sensory neuronal hearing loss, has eight compounds targeting KCNQ4 in its pipeline.
Company website here (comment: Acousia seems to keep a low profile, so for now don’t expect to find any additional details about these eight compounds): http://www.acousia.com/
Last but not least, a fun fact.
Aside from the repurposed drugs that might hold hearing restoration potential, there is another compound related to KCNQ4 mentioned in the paper. An exotic one, as described in one of the cited papers: Subtype-Selective Activation of Kv7 Channels by AaTXKβ(2–64), a Novel Toxin Variant from the Androctonus australis Scorpion Venom.
Scorpion venom. Hmmm…
AUTHOR’S NOTE: There is something oddly reassuring about the thought of researchers from around the world leaving no stone unturned (and no tiny venomous creature unexamined) in search of a potential hearing loss cure.
A good reminder that we never know where (or from what) the next big discovery will arise. Nature is full of secrets and science is constantly uncovering these surprises…
More updates to follow…
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