New University of Michigan Tinnitus Discovery — Signal Timing

Are you able to link what you are taking - sleep is a big problem for me.

 

Do you guys think that Dr. Shore will release the device in 2023?

 

As I said, the only scientific proof we have of a particular region causing tinnitus is the work regarding the DCN and the action of Fusiform cells in particular. Apart from myogenic and TMJ I suppose.

 

DCN is just a part of the cochlear nucleus. That's the problem. With tinnitus one can only assume that the other parts are altered as well. I believe that working on modulating higher stops of the auditory nerve in its way to the auditory centers would handle much better the problem and even eliminate it.

 

How can we distinguish between normal sound and tinnitus or do we just want to reduce overall activity?

 

I'm not sure that I understand your question, but tinnitus free means hearing silence and external sounds only. You will recognize it for sure. What I think will be weird is to find yourself again in that situation, after being tormented with tinnitus so much.

 

Cochlea based tinnitus will create activity between the cochlea and the brain but so will normal sounds as well. How can this only stop the activity from the overexcited neurons?

 

The right modulating electricity device would put the signal in order. So the neurons will fire when there is an outside signal only.

 

Can someone explain why it takes months and even years to publish research results?

 

It's a number of factors. In some areas people don't trust publishing preprints (because they are afraid someone else will steal the idea, slightly change it and send it to a journal), so they are only happy when the paper has been peer-reviewed and published in a journal to come out and announce results. If the peer-review says major revision, the revision can take months or years. At times reviews are very idiosynchratic and driven by personal feuds and rivalry rather than by actual merit, and often it depends whether the authors are connected in some way to the editorial board or not. If the authors have to humor reviewer's strange requests it takes longer and longer. Worse, if the first one or two journals reject the paper and this has to be submitted and reviewed several times, this may end up taking years.

It's not always this bad, but it happens. In my view, given that universities are often funded with public tax money, the research should be immediately made available to the public in form of preprint, before the peer review, to the point that some academics particularly interested in the area could do a spontaneous peer review and contact the authors, and be updated after the journal peer review anyway. Some countries are considering this model. It is common now in physics and maths for example to put the paper out as a preprint in arXiv.org, although again this is not a fixed rule. But the overall result of this is that, when authors do not release a preprint, it may take years to see the published version and everything is delayed.

Susan Shore seems to be against this preprint approach and only wants to publish the paper once it has been peer-reviewed. I hope she has good relationships with the editorial board of the journal where she is submitting and that the reviewers don't get lost in bizantine requests, so that the paper comes out ASAP, but what she should really do, being paid by a university that should work for the public, is to release a preprint with the preliminary results and update it later with a journal paper. Pity she won't do that and people will suffer or die for the delay.

 

Again here the rough analogy with phantom limb syndrome could help. Assume a patient has lost two fingers. He will feel the remaining three fingers but will also have pain sensations from the two missing fingers. The brain is looking for those fingers and not finding them generates pain signals. However, if the two missing fingers could be restored, it is possible that the wrong plasticity of the brain would reset and the phantom pain go away.

It is maybe possible to bypass all this if one can shut off the overfiring neurons corresponding to the missing fingers if it is not possible to regrow them. The analogous would be, roughly, the DCN approach of Shore. She would shut off the overfiring neurons without restoring the cochlea. This way one would maintain hearing loss but would see tinnitus diminish.

This is the theory, to see if it works it seems we have to wait for Shore's rituals, sadly.

 

The sad thing is the most encouraging personal anecdotes shared here related to this kind of treatment originate from the University of Minnesota device, a research project which has since wound down.

While I think this kind of treatment has potential, effectiveness seems to be wholly dependent on the treatment regimen, i.e. the nature of the actual stimulation. That would explain why Lenire doesn't work but Minnesota and Susan Shore's approach does (or seems to).

So I don't think it's time to write off this approach completely. We have to see whether "Auricle" actually pans out when it eventually materializes.

I think the branding/commercialization plan with Shore demands that it finally exits the lab within a reasonable timeframe. I predict it will start trickling out in some limited numbers by the first half of 2024 although the average sufferer here probably won't be able to get it until much later, which may be all the better as we need to wait for early word of mouth of early adopter "beta-testers" ala Lenire.

I certainly don't want to suffer "disimprovement" as some Lenire users did--to devastating consequences. This kind of treatment is more risky than people here are willing to admit.

 

What brand of probiotics did you take and what was the dosage?

 

I still don't see the relationship between results in a journal and FDA clearance. Is it a prerequisite or leg-up?

 

I believe Dr. Dolittle helped with the animal models.

 

I wrote to Jon Pearson recently. Here is his response:

Thank you for reaching out, and for your interest in Professor Susan Shore’s tinnitus research and the company that was established to gain regulatory clearance for and then commercialize Susan’s novel device. I apologize for my tardy reply, but I make it a point to respond to all tinnitus sufferers that reach out to me directly, and you can imagine that I get a high-volume of inquiries.

We attempt to balance the provision of information with the need to handle confidential and non-public data with appropriate care. While we understand the desire of chronic tinnitus sufferers to want to know when a treatment will come to market, how much it will cost, how well it will work, and where it can be obtained, the reality is that most of these questions are not answerable today, and it is actually a disservice to sufferers to attempt to pre-empt the many complicated and challenging steps of regulatory clearance and then commercialization by providing off-the-cuff guesstimates. This can lead to frustration, which then causes distrust in both the research as well as the company attempting to bring the innovation to market.

Perhaps some perspective on the time domain is helpful. Professor Shore started her tinnitus research in the early 2000s. The initial years of research were on animals (‘pre-clinical’ research as the precursor to human trials), and the first human pilot study was not peer-reviewed and published until 2018. This means that nearly two decades elapsed until the first human pilot results were complete. I co-founded Auricle in 2019, funded the company on my own initially, and obtained outside funding in 2021. Please note that universities perform research and develop ideas, but that it is the work of companies to bring those ideas to life. Although the human pilot results were extremely promising, those results were on just 20 subjects with a prototype medical device. The second human trial will indeed conclude soon, but we must be careful in determining when those results are assessed and made public as there are stringent rules concerning the publication and dissemination of clinical trial data that may be used as part of a regulatory filing. As such, we will not be making public pronouncements that may compromise our ability to prosecute a regulatory clearance.

While the pace of developments may be disappointing, there is nothing about this process that can be forced or sped up—we are doing all that we can to focus resources on working with regulatory bodies to gain the necessary clearances so that we may one day bring a proven therapy to market. Given the lack of therapeutic tinnitus treatments—device or drug—regulatory agencies like the FDA are exceedingly (and appropriately) cautious in evaluating emergent therapies. I have spent my entire career commercializing medical devices, so I am familiar with the long and challenging pathway ahead, but I am CEO of this company—and have dedicated my career to it—because of my belief in the strength of Professor Shore’s research and our common desire to bring relief to the millions of global tinnitus sufferers as quickly as we can.

I know that what I’ve written doesn’t answer your questions, but I’m hopeful that you may understand that we are deeply involved in a complicated and challenging process that has no guaranteed outcomes for anyone. We are hopeful, however, and would like you to remain so as well.

Kind regards,
Jon Pearson
CEO & Co-founder
Auricle, Inc.

 

Thanks for reaching out to him, @DebInAustralia. If anything, my takeaway from his response is that it might take even longer for this to get to market than I previously thought. The part about Susan Shore’s research beginning in the early 2000s and human clinical trials not beginning until ‘18 seemed to imply that time is “cosmic” when it comes to the process of getting a medical device on the market. What I mean by that is, like the universe and its development, eons of time is nothing. But who knows? We’ll have to hope for the best. And hope the results are good.

 

Thank you for sharing this with us Deb.

 

Thank you indeed, Deb. Unfortunately, this answer doesn't explain anything. Why did he state last Fall that the device was nearly market ready? Why did Levo and DeSyncra obtain FDA clearance easily when they proved to be completely ineffective a posteriori? Have the rules tightened? Why does it take so long to unblind the results? Does the FDA require a peer reviewed publication or can they review a write up of the results themselves?

This reply sounds a lot like "you folks can't understand how complicated this is, so just sit and wait", ok maybe guesstimates would be a disservice (but isn't this what he did last Fall?) but why not explaining a little more what are the concrete steps that take so long now that the unblinding is under way?

 

What I said in a previous post, and included a link to it, is that the first stop, the cochelar nucleus, contains more parts, not only DCN. My thinking is all of the overfiring neurons in the whole cochlear nucleus should be shut off.

 

I tried 3 different probiotics and they all made me sleep way better. I used to sleep 3-4 hours a night, now it's more like 7 hours and that happened quick. The first two brands gave me stomach issues, but like I said I slept much better on them. The 3rd one I provided in the below link is the one I take now.

Start off at 1 pill a day for like a month, then increase to 1 a day & 2 the next day, and keep going 1, 2, 1, 2, 1 and so on. Then if it works, go to the full 2 a day.

Amazon.com: Nutrition Now PB 8 Probiotic Acidophilus For Life* Vegetarian Dietary Supplement for Men and Women, 120 Count : Health & Household

I think this probiotic didn't give me stomach issues because it is low in active cultures if I had to guess. It has 14 billion active cultures while an average probiotic has like 30-50 billion...

I hope it works for you, but everyone is different. Definitely try it though.

 

This means... nothing (?).

 

You may be right. I hope you are wrong, or Shore's device will have limited effectiveness. Anecdotally, we know it helped @linearb, but a sample of one doesn't help much.

EDIT:

There are some old papers of Shulman that analyzed the brain pathways activated by tinnitus, using SPECT imaging. This led him to recommend Gabapentin plus Clonazepam, as a synergistic strategy to calm down said pathways. However, I don't think there is a unique model. For some people Clonazepam dramatically silences tinnitus, for others it only calms anxiety. I'm in the second camp. So who knows what brain structures are involved really. It would be good to know if there is any evidence Shore has to believe that most of the action is in the DCN, but I have to confess I'm too ill to read her papers.

 

I know, obnoxious isn't it?

I find it kinda poorly written to talk about it being a disservice and would only cause frustration if this or that happened in his response. There is going to be frustration no matter what.

 

Luckily a sample of one, when one is @linearb, is better then most. He has been a long time, great addition to Tinnitus Talk. I know you aren't saying he isn't.

Just gives more hope than a random person showing up and saying this worked, maybe or maybe not answering questions and then moving on.

 

This paper says what I said, this is how I see it!

https://www.sciencedirect.com/topics/medicine-and-dentistry/cochlear-nucleus

That's why this kind of device can work better for somatic tinnitus.

 

I think what's ocurred with Susan Shore (and many other medical researchers quite honestly) is that because she's arguably part of the first generation of people evolving their science in the Internet social-media era, a seemingly localised interview she gave in 2013 that might historically only have done the print rounds within the research establishment has the power to gain traction and become globally distributed via the new medium. And this brings with it all kind of issues.

The Internet can be a real double-edged sword. Advertising over the years has convinced many people that everything can now happen at lightening fast speed, which may be true where downloading a movie is concerned but couldn't be further from the truth with medical research that just plods along at it's own pace like it always did.

Editorially I think U. Mich. should try to learn from these kind of situations with 'new media' and perhaps be a bit more conservative in their public approach. Obviously it's important to inform people about exciting new projects but they do need to balance this with the reality for the clinical end-user particularly when the potential consequences can be as catastrophic as those we've tragically seen this past couple of years.

 

Is that what you asked @DebInAustralia?

All we want to know are the results of the completed study.

Was one of those questions: can you provide some results of the study soon after all the final data have been collected?

 

I share your frustration.

I asked the following:

• If they can release any preliminary data?
• Why they announced that they were nearly market ready prior to trial end date?
• If they have applied for FDA fast tracking?
• International patents?
• Why do we need to wait for an update in the Summer?
• Why is unblinding now being pushed out till next year?
• When will the results be published/announced?
• Can anyone apply for compassionate use of the device given the urgency of this research?

I do have a contact with one of Susan Shore's PhD students from the earlier trial. She has reached out to Susan, and am waiting to hear back from her with any updates. However, I am not overly optimistic about what she can reveal at this point. I was made aware that results need to be published (according to this contact) within 30 - 90 days of listing the trial details on ClinicalTrials.gov.

I'm sorry I couldn't get much more than that.

 

Well done Jon, one of the best political corporate BS I've ever read, hats off. 2 pages meaningless email.