Inner Ear Hair Cell Regeneration — Maybe We Can Know More

Sadly, I agree. I'm wondering if and when trials will start, and if it could receive further funding. However, I'm not sure if drug development can be sped up by the EU's regulatory bodies in the same way it can in the US by the FDA.

 

SIU scientist receives DOD grant to advance hearing loss treatments

 

The future role of artificial intelligence in hearing disorders. It talks about how hearing has fallen behind in this respect.

Harnessing the power of artificial intelligence to transform hearing healthcare and research

 

We can know more, BUT...

Today I took part in a focus group about a type of hearing regeneration. It is a solid partnership of established scientists, universities and the health service.

Whilst I cannot provide any details whatsoever of the companies, trials or scientific particulars (confidentially agreements), I can hopefully put a realistic picture of where hearing regeneration, whether stem cell or genetic engineering, is currently.

I joined Tinnitus Talk a year ago, right in the middle of OTO-413 and FX-322. I read through the threads and was full of hope. It seemed easy, Phase 1, then quick readout, Phase 2, another quick readout etc and it will be on the market in 2026. This was naive of me and many others, and today more than ever it hit home.

Headlines of "key breakthroughs" are sometimes exactly that. But that key discovery is a computer based model or at most a petri dish finding. In other words it's a couple of years at least from animal trials.

Trial length and follow-ups. Any time new cells enter the body, they carry risks. If a cell doesn't do as its told and proliferate into auditory neurons or hair cells, the risk is cancer, allergic reactions and autoimmune attacks. Follow-ups therefore need to be YEARS AFTER the trial procedure has finished. 5 years seems reasonable. Then you plan for a Phase 2 and recruit participants etc.

You can see where this is going and why it's such a long process. This is if it's showing safety and efficacy. Then it needs approval and then to come to market.

So whilst it's certainly looking possible, 10 years seems wildly optimistic, and 15 years realistic with a positive attitude.

So the upshot is it is not on the immediate or short term horizon and if you need hearing aids or a cochlear implant, you should get them. I have said it before that technology will arrive first and is already well ahead.

After the antics of some biotechs, I hope that we can look realistically at the future of hearing regeneration and also guide newcomers, who like me were a little gullible and misled by those whose aims are to make profit and increase share values. Luckily this focus group didn't contain such entities working on behalf of hearing research.

Science works by challenge, and some of the hype really suppressed the debate that was needed, particularly in the Frequency Therapeutics thread. People were burnt. The question is, who is the next wolf amongst the sheep? Spiral Therapeutics immediately rose its head above the ashes of Frequency therapeutics failure, bought Otonomy's failed product and started engaging with the community. Given what I've shared, be very, very wary.

So, yes I believe hearing regeneration is a great step for tinnitus treatment, however it's a long way away, and today, from speaking with a couple of researchers, it hit home.

Here's to effective treatments for tinnitus and hyperacusis!

 

You know what else hurts? I still think FX-322 wasn’t a complete failure, they just needed more time and research but unfortunately ran out of cash.

*sigh* hang in there dudes. One day...

 

Thanks for the detailed write up, mate. Yeah, this past few years have been a bit of a rollercoaster ride where all this new injectable business has been concerned. I think the Internet puts us in this slightly strange headspace where because we're almost privy to the minutiae of what's discussed around the water cooler at Frequency Therapeutics we conflate that with an impending breakthrough available at the point of care, which is clearly very very far from the truth.

For what it's worth, my money is still on the mechanical tech; the kind of stuff Susan Shore, Hamid Djalilian, and Heidi Olze are involved in because in principle a lot of the precursor devices to these pipelines (cochlear implants for example) have already demonstrated anecdotally to ameliorate tinnitus. I genuinely believe we'll see a real breakthrough in that field within our lifetime.

 

Well that's cheered me up for the start of the weekend

 

It was a two and a half hour focus group. 5 patients with hearing loss and 2 researchers involved in the programme.

The good news is they have done numerous preclinical work and the cells proliferate into the intended cells. However, you still need to monitor patients over a period of time so they don't suddenly start expressing themselves into something undesirable. The cells in question are to regenerate the auditory nerves that connect to the inner ear cells. These are often lost due to age. The design of the clinical trial is solid and the support thorough. It is something that is scheduled to start end of 2024/early 2025. Very small pilot study at this stage. I do not speculate on here as to the partnership, but if you have an idea, then you have an idea. Let things unfold.

I just wanted to give a realistic overview that was not specific to the content of the focus group per say, but it gave me a solid idea of where we are.

I have read people say they are "holding out" to see if FX-322 or OTO-413 works etc. After today I cannot see how these companies can be serious and professional about bringing something so unknown and new to market with hasty readouts and very limited follow-up. It seems the participants are discarded after data collection, with no follow-up. I think the problem with these types of biotechs is they want to keep investors hooked and excited and to move at haste.

If a drug was in clinical trials, then a shorter follow-up might be acceptable. Many side effects are acute in nature and most medications are eliminated from the body within 7 days. In those scenarios you can race through the clinical trials if efficacy and safety is OK. But something where you are growing and altering the structure of pre-existing anatomy requires long-term follow-up.

I did feel disappointed at the timelines because I realised I was in a group with 2 researchers who have spent years in preclinical work and expect positive results. They are not beholden to shareholders and their goal is bringing about a brand new treatment.

Our focus has to be on looking at what's available now and generally it's unsatisfactory. The nearest treatments look likely to be bimodal stimulation and forms of non-invasive electrical stimulation, with some potassium modulators appearing around 2025/2026, which may be hit and miss at best with subgroups of us getting a bit of relief from any of the above. We need a couple of people on Tinnitus Talk to get their hands on one of these potassium modulators, whether through an early safety trial or compassionate use.

Other than that, we may get a surprise from SAGE-547 or Pimozide, but I'm not enthusiastic about these like most of you here.

With the extracochlear implants I'm surprided Cochlear Ltd or Med El haven't seen the opportunity here. The market for this type of tinnitus treatment is larger than the hearing restoration for deafness.

It didn't cheer me up. My tinnitus was screaming from the laptop sound as I sat through the meeting. I was really struggling. But when does optimism become delusion? I have some optimism for the Dr. Shore's device because some subjects have proven it works for them.

 

This is an extremely gray and sobering comment. I hate that you're so spot on with this, realistically it will take 15 years and that's if we're lucky. Shame really. Hoping that some drugs that are in the pipeline can at least quiet the tinnitus while we wait for regeneration to help us.

 

Or it points us to focus on other alternatives that will be available sooner. Think of it this way, whilst everyone was focusing on OTO-413 and FX-322/FX-345, Auricle (Dr. Shore's device) was proceeding through a successful Phase 2. There are other treatments in work that will not take 15 years to be widely available like electrical devices and possibly even drugs. All it means is we refocus a bit. It's still worth following the stem cell and genetic based treatments for sure, but with an understanding of likely time required to bring something to market. If you can get in a clinical trial, then you could potentially access a treatment earlier.

 

I just saw Dr. Djalilian two days ago and my experience is very similar to another member's. Basically his instruction is to take vitamins and Nortriptyline. When I inquired about sleep solutions, he told me to see a sleep specialist.

 

Wow. You didn't question him on his extracochlear stimulation treatment then? I guess the Nortriptyline suggestion is based on one study showing it reduced tinnitus loudness by 10 dB.

 

It doesn't surprise me to be honest. I think in their day-to-day clinics at this point in time people like Dr. Djalilian are going to suggest to a patient what they believe will help now and is available. I'm sure if I visited Heide Olze she'd suggest similar.

Did you get to talk to Dr. Djalilian about his research? The interview he gave Tinnitus Talk was intriguing.

 

I did ask Dr. Djalilian about his clinical trial and electrical stimulation (sorry if I didn't use the correct term). He said they are working on it.

To be honest, he seemed really busy and told me to get fitted for hearing aids and take the Nortriptyline. He said that is the solution for me. I filled the prescription and am afraid to take it.

I can send him a message and see if he will respond. I do have an appointment with the audiologist coming up.

 

I can't seem to find Dr. Djalilian's Tinnitus Talk interview. Was it recent? Do you have a link?

 

The Man Who Donated a Million Dollars to Tinnitus Research

 

Some new findings from University of Virginia:

UVA Scientists Discover Repair Process That Fixes Damaged Hearing Cells (virginia.edu)

 

Where were they discovered? Mice? Zebra fish? Petri dish?

 

Looks like mice.

Repair of noise-induced damage to stereocilia F-actin cores is facilitated by XIRP2 and its novel mechanosensor domain

 

It would be very difficult for a focus group w/ only 5 subjects to give meaningful results. Back in the day, I was a recruiter/dept mgr for 2 large US market research companies: Fleishman Field Research in San Francisco, CA, and KCA Research in Alexandria, VA. Our clients were almost always medical groups, drug manufacturers, the EPA or OSHA. For OSHA, our study required 5,000 businesses across the US. For the medical focus groups in S.F., we usually needed at least 10-20 carefully chosen respondents, and triple that for the drug makers. 60 people were broken up into groups of 15 for 4 days.

The results were actually tabulated within a day, then sent to the clients. It was very straightforward and had to be within the same variables each time. We also recruited doctors for focus groups, which were always done on our site. Everything was observed and visual/audio recorded for ALL the focus group respondents through two way mirrors. They knew that, but seemed to immediately forget it once things got going.

W/ the doctors, this meant getting them away from their offices from 7:30 AM to 8:30-9 AM on Saturdays so they could make their reserved tee time on the golf courses, LOL. We set the parameters for the questions after the clients told us what they were after, then the clients would OK them. Usually w/ revisions, sometimes not. We also had to pay the doctors quite a bit of money in order to persuade them to participate. We paid all our respondents (or they wouldn't come), but the doctors got a lot more or you could forget about them even going through the qualifying questions on the phone.

Doing this 5-6 days a week for several years, we finally came to realize the clients already knew what the results should be, which is why they wanted particular questions asked in a certain way. Since they had to present everything to their Board of Directors for approval, they saw little use in giving them something that was just going to be rejected.

 

I hope it‘s seriously news:

Some Deaf Children in China Can Hear After Gene Treatment

 

The treatment will not help everyone who is deaf. It applies only to one specific cause of deafness at birth: a defect in a gene that produces a protein called otoferlin. The inner ear contains about 16,000 hair cells, so called because they have comblike extensions that vibrate to different frequencies of sound. Without otoferlin, these cells can’t transmit the chemicals that relay information to the brain.

 

STR001 reached Phase III. If efficacy and endpoints weren't met, they'd have pulled the trial in Phase II. It would be nice if anyone from the clinical trials was around here haha, or if we could get a response from the company which is still showing active and maybe in the late stages of liquidation.