The Association for Research in Otolaryngology (ARO) 2023 MidWinter Conference

The largest research conference in Otolaryngology will take place on February 11-15, 2023: → the 46th Annual MidWinter Meeting of Association for Research in Otolaryngology (ARO).

It is a 4-day event with a ton of new publications and results.

I separately posted → some results of Acousia Therapeutics and → some research news of Ebselen but there is much more on hearing regeneration, hearing loss, tinnitus, and hyperacusis at this research conference.

You can click on the day/time slot and then click on the presentation for more information/abstract. You can also find the results which are going to be presented. I'm not going to copy paste 100+ results but you are feel free to highlight here the ones that are important.

 

This is really great news. REALLY great. I will be making another small donation in January as I'm skint at the moment with Christmas and cost of living bullshit in the UK.

 

Wow. Now that IS a turn up for the books. His 2011 paper massively influenced my own thinking about what tinnitus is and how it's generated.

The idea of dysfunction in an upstream gating mechanism that essentially allows the tinnitus percept to 'leak' over into consciousness is the only explanation that's ever made sense to me.

It certainly would explain why some people with hearing loss get tinnitus whilst others don't (I've never bought the 'hidden hearing loss' theory).

Would love to hear Josef Rauschecker's current views on his 2011 paper and whether his perspective on it has changed. If you're able to get those views on camera, that would be a real scoop.

 

While any information on Josef Rauschecker's research is of high value, the most relevant for those with severe tinnitus might be near-term prospects such as deep brain stimulation.

In your last interview with Dr. Rauschecker, the latter was unfamiliar with Dr. Shore's work. Wonder if that has changed.

 

For a long time, I thought his theory made the most sense. But if you think about it, it falls apart with all those diseases that sort of "force" tinnitus as their symptom. For example, all patients with Meniere's, otosclerosis etc have some kind of tinnitus, so you would think that some of those people would have the stronger gating system that doesn't allow tinnitus to reach consciousness.

Rauschecker's theory explains the cases of unknown origins, noise or stress induced, but it doesn't say anything about those other diseases. I have also learnt from around here and from a neuro-otologist I visit, that noise and stress can cause events like hydrops in the inner ear, so things get even more complicated.

I agree, though, it's a huge thing to search why some people with hearing loss get tinnitus, while others (even with big or sudden losses) never get it.

 

I'd love to hear from Acousia Therapeutics. They are targeting KCNQ4 potassium channel cells in the inner ear for several forms of hearing damage, the latest press releases shows Q2 trial starting early 2023 so they are moving fast.

 

Hi Hazel,

They are there. A bit tricky to find in the conference as they do not present under Acousia but under ACOU085.

Hearing loss company Acousia Therapeutics to present data for lead candidates ACOU085 & ACOU082 at ARO 2023 MidWinter Meeting February 11–15

Name of the poster presentation:

SU141 Small-Molecule Kv7.4 Activator ACOU085 Protects from Cisplatin-Induced Hearing Loss and Outer Hair Cell Death in a Guinea Pig Model

 

Would be great to know if tinnitus is one of the indications of ACOU085 or ACOU082 and timeline for clinical trials. Both molecules are for noise/ototoxicity induced hearing damage with purposes of managing chronic hearing loss as well as future damage so very curious how they will look at tinnitus and if this will be a secondary endpoint in their clinical trials. Many thanks!

If you talk to Jonathan Kil of Sound Pharmaceuticals, of course we are very curious what the anecdotal evidence is so far for SPI-1005/Ebselen for tinnitus and not just Meniere's disease, and what their timeline looks like for completion of Phase 3 and potential market submission.

Dr. Susan Shore's 'team' is also there. Nothing specific to ask, any news is welcome, but I'm really interested how they interpret the results and if they are satisfied with the outcomes or if they were expecting more.

Very nice that you travel there, I'm assuming that air travel/sound does not impact your tinnitus. Your itinerary seems noisy

 

First poster I'm interested in:
Poster Session 1: SA225 Drug Discovery for Noise-Induced Tinnitus Based on the SBAD Model (Joseph Pinkl, McKenzie Rice, Jianxin Bao)

Particular questions: What's the development stage of this treatment? Is there a timeline for upcoming milestones?

Second poster I'm interested in:
Podium #13 - Synapse and Auditory Nerve in Hidden Hearing Loss
Transtympanic Delivery of Soluble Fractalkine Peptide Repairs Cochlear Synapses and Function After Acoustic Trauma (Vijayprakash Manickam, Andrew Stothert, Elyssa Pereyra, Lyudmila Batalkina, Tejbeer Kaur)

Particular questions: What's the development stage of this treatment? What are the results from the transtympanic delivery of "Soluble Fractalkine Peptide"? Can you visualize the results? Is there a timeline for upcoming milestones?

 

Hi @Hazel, the above link didn't work my side. Anyhow, I've been to the site and searched for sessions specifically covering gating. Did you mean this one?: Link to PDF here.

Looks like a fascinating study. I wasn't even aware University of Canterbury had been involved in this or are even ready to release interim data.

 

❤️️

 

@Damocles, really generous of you man!

 

@Hazel, if there is time, I think reaching out to AudioCure would also be very helpful. We don't have a thread on them yet here on the forums but they are working on an injection that targets to reverse hearing damage/regenerate synapses. It is currently in Phase 2 in Europe. It is very much under the radar. Pre-clinical studies showed almost complete reversal of acute hearing loss. It also targets acute tinnitus. They have EMA orphan drug designation. They will present Phase 1 data at the ARO. Perhaps some questions on timelines and outlook on specifically recovering from chronic vs. acute tinnitus?

https://www.audiocure.com/newsroom/news-in-brief/

The primary focus of AudioCure’s development program for AC102 is acute hearing loss and acute tinnitus. Currently there are no approved drug treatments available for these disorders. Our front-runner molecule has undergone comprehensive preclinical research which demonstrates that it acts upon the sensory cells and neurons with their connections that are central to the hearing process. As no other drug has shown any such action, AC102 has the potential to become the first breakthrough causative therapy (i.e. treatment aimed at eliminating the cause) for acute hearing loss and acute tinnitus. By treating these conditions as soon as possible after onset, it is our vision to prevent the development of long-term, chronic hearing impairments.

How AC102 works
In acute sensorineural hearing loss, the sensitive structures within the inner ear which are critical for the hearing process are damaged; namely the inner and outer hair cells and their synaptic connections to the auditory nerve. Preclinical studies have demonstrated the unique potential of AC102 to tackle the damage to these key players.​

 

Hyperacusis: Results of a Novel Treatment Approach

Please ask them what their scientific source is when claiming that protection against painful sounds worsens one's hyperacusis.

Spoiler

There very likely is none.

 

I can’t say I’m surprised, but it’s still embarrassing to see. Have they ever attended an ARO conference? You would think the bigger organizations for tinnitus would attend one of the largest and important research conferences for tinnitus...

BTA/ATA feel like outdated organizations. There’s a stark contrast between them and what Tinnitus Hub does IMO, yet they get all the money.

Nice donation btw, @Damocles.

 

Hi, this ARO looks particularly good!

The presentation regarding the BK channel modulator also fit a theory I already had; glad to see research being published about it.

The Presentation is presented by Celeste Ferraguto.

SA181 BK Channels as a Therapeutic Target for Auditory Impairments in Neurodevelopmental Disorders: Preclinical Findings From a Mouse Model of Williams-Beuren Syndrome.

I don't know if they will be there since it is just a poster presentation, but they are putting the poster up on Saturday, February 11.

The question I have is two-parts.

Part 1:

Given the positive association on BK (which make up the fast afterhyperpolarization current) potassium channel in hyperacusis present in neuro-developmental disability, what are the authors' thoughts on the findings of Prof. Thanos Tzounopoulous, that the main constituents of the medium afterhyperpolarization (Kv7 and HCN) currents have been found to be dysregulated after the onset of tinnitus?

Part 2:

In consequence of the findings of the presentation, physiologically, It is now known that activators of fast afterhyperpolarization current, and medium afterhyperpolarization current can act as a mechanism to attenuate hyperexcitability in the aduitory system. Given that the perception of sound, like any other sensory input, is transmitted through the neurons, as an electrical action potential, is it possible that activating afterhyperpolarization current in general could serve to control burst firing and action potential trains which we experience as the percept of hyperacusis? This would be a very thorough physiological explanation for the condition which lines up very neatly. If so, activation of the slow afterhyperpolarization current would serve as a potent inhibitor of burst firing and action potential trains. And thus, hyperacusis. Thoughts?

 

And, is the cure there yet???

 

You can use the hashtag #ARO2023 to see some highlights going up live.

 

More awareness for hyperacusis is always good.

 

Thanks @Hazel! Can’t wait to see what you can share from Dr. Rauschecker!