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You condition the animal to do a certain behaviour when hearing sounds. For example the animal gets electric shocks shortly after a sound is played, or the animals get food at a certain spot while playing a sound. After one induced noise to the animals, they will behave different to the control...

To explain it very quickly: Some papers showed, that NHPN-1010 increases the BDNF concentration (not sure whether studies where animal studies or on vitro). By this, synaptic growth is enhanced and hidden hearing loss hopefully treated (basically in the same way as OTO-413 intends to). As long...

I can totally relate. My tinnitus changed from mild to 24/7 in the last 6 months of my studies. The final worsening happened only days after graduating. I know the feeling when suddenly all the hard work one has done to get to this point becomes suddenly meaningless.

I would still be very cautious as to put too much hope into SPI-1005. What made me wonder in the last weeks is the death of Kent Taylor. SPI-1005 and HPN-07 would have been easily available for a millionaire and surely one tries everything before going into drastic measurements. Obviously if...

This would have made sense if I had used an e-commerce platform or for example PayPal. But this was old school just via email (I found the supplier using chemicalbook.com) and bank wire, so there would have been 0 chance for me getting the money back in any case. Also I have to say that they...

I did not even have to test the sample (I still will for sure, simply because I have access to NMR spectroscopy). Basically the package I got sent contained a cheap foundation ingredient of cosmetics and all the declarations for customs as well as the shipping invoice stating the same. Since...

As a warning to everyone trying to order Ebselen or other chemicals from China: Request first a sample to test for a low price before ordering a larger quantity. I ordered from a Chinese supplier a probe to check and it turned out to be scam. So even if you are provided with legit NMR, HPLC...

As far as I know it has not even started yet. According to this website it will probably be completed in April 2023...

FX-322 was great as it had the promise to cure the problem at (one of) its roots and also because it was being developed rapidly. After the disaster with FX-322, we should lower our expectations. SPI-1005 will at most alleviate our problems, but not cure them. The beauty of SPI-1005, on the...

Jumping on the habituation bandwagon maybe?

The whole situation stills feels so unreal. I also still cannot get over the fact how FREQ acted so positively over the last weeks and the results have been so bad. Do we have a guess since when have they had the data on their desk? It' s just crazy that they released the paper for Phase 1 with...

I still have the feeling we have not consolidated on a clear statement what to make out of the results of the Phase 2. Agreed: it was a disaster compared to our lowest expectations. But what does that mean? Is the whole concept of the drug failed? Is the delivery of the drug failed (even more...

I guess most of us had a hard time believing you since your statements have been very enigmatic and without (solid) proof. May I ask since now all the dust has settled what your sources for your guess have been? Did you kind of had solid proof or was it all just a very sophisticated guess...

I agree with you - besides the two days when I woke up with sudden deafness in my ear, this is the worst day of my life. 2021 did start so well with potential readout for OTO-413, hopefully good news for their drug against Meniere's and the readout for Phase 2a of FX-322. Now Otonomys Meniere's...

Did we already see the extended audiogram changes? I mean it is plausible that more injections do not help with the lower frequencies, but maybe at least more injections benefit the higher frequencies... I think the most important question will be whether they will commence Phase 3 regardless...

If you are interested in synthesising, here are the different ways of synthesising it: https://www.pharmacodia.com/yaodu/html/v1/chemicals/2d1bafe55b0b49961617e5b71cbb1292.html In principle it should not be that hard to do it. I guess the main problem is, that you need a complete laboratory...

So your lowest "dip" is 5dB? It is just very surprising to me, that such a low dip can cause tinnitus. The only explanation I could have is that hidden with the loss in the audiograms is a much more significant synaptic hearing loss. Or maybe a very sharp dip, which could not be resolved within...

Does anybody know the approximate bioavailability of Ebselen when taken orally? I've skimmed many papers about Ebselen but so far I could not find any statement in that regard.

If your lowest dip in standard audiogram is only 5 dB then probably this won't be the cause. Have you checked your higher frequencies (above 8 kHz?). You might have there much more hearing loss without even knowing. Regarding whether FX-322 will help below 8 kHz: We do not know so far and...

For some reason Les Misérables' "One Day More" (caution: link leads to a song on YouTube) really comes into my mind when thinking about what might be about to come. Really hope we get our own revolution in some sense...

I just found this paper about the clinical trial of SPI-1005 where they evaluated its efficacy for preventing NIHL: Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial Interestingly, the 600 mg group...

If he had sold because he already knew something about the results of the clinical trial(s), this would have been insider trading — which is highly illegal.

I hope that they will continue Phase 3 even with these "bad results". If they can show that high frequency hearing regeneration can significantly increase words-in-noise and word recognition, then they have still a product for an unmet medial problem. So hopefully continuation to Phase 3 and at...

The current consensus is that the current delivery method will likely work better for higher frequencies, since not enough of both molecules (but especially VPA) reaches down into the cochlea. My guess is that already 8 kHz will be borderline working, but in the end only the results of the study...

Another reason might be that VPA alone could also deplete support cells (see @Aaron91's post in the Pipeline Therapeutics thread). So maybe it is even on purpose that the VPA concentration drops faster as to make sure that VPA cannot reach cells without CHIR99021.

In the Frequency Therapeutics thread there was a vivid discussion about the VPA concentration dropping much faster than the propriety molecule. If VPA alone really depletes hair cells, maybe the asymmetry in concentration is on purpose to avoid a surplus of VPA depleting the support cells.

Thank you very much for the reply! I really like how they show the comparison between BDNF (OTO-413) and HPN-07. If HPN-07 (+NAC) really has the same effectiveness (provided the concentration is adapted correctly) as BDNF, this great news.

Can you maybe provide me some sources for this? So far I have not found any clear statement for it (I did not find any so far - except for the podcast), so I would really like to get a more in depth answer...

But do we really know for sure that the ‘bomb blast’ pill by HEI is also repeating/creating synapses? I have listened to the Tinnitus Talk Podcast, where they talked about it: "Then, subsequently we found out that it might have some restorative capabilities and may have some efficacy for...

For me personally, having the loudest tinnitus is not really a competition. No matter how we got tinnitus, no matter what the true underlying mechanism is, we are all in this together - trying to cope with it, trying to understand its nature and finally trying to get rid of it again.

I guess most Tinnitus Talk members who invested in FREQ have done it for the long run. We all know that investing into Biotech is risky and if they fail their trials, the Stock might drop significantly (frowning at OTIC). I agree that we should not already hope that the outcome of the current...

Considering the series of bad news from Otonomy: what are our alternatives of drugs curing already existing and chronic synaptic damage?

If the current trial shows only improvements above 8 kHz, they could still make Phase 3 and bring it to market afterwards, or am I mistaken? In this case we will have FX-322 already in 2023 but it will only help a special subgroup of us. I think it is clear, that they will try to make a better...

The good thing about this trial is that it will show whether IHC and OHC will be fixed in the areas where FX-322 does reach. If it significantly increases the audiogram in the area above 8 kHz it may mean that only the delivery method needs to be refined. Without deep understanding of the topic...

Out of curiosity: Can't we use the pharmacokinetics model of FX-322 as a basis to assume how deep OTO-413 might reach? I mean if we compare the typical time for the VPA to reach its peak at ~2 kHz (roughly at 3 hours) and compare it with the slides from OTO-413 from December, where the...

Probably not the right channel but: Is there already any consensus in the community as to whether NHPN-1010 (HPN-07 + NAC) has any ability to regrow synapses just as OTO-413 is supposed to have?

As there is always a lot of talk about the astronomical prices of the molecules involved in the drugs (most notably for SPI-1005 and HPN-07): The prices on Sigma Aldrich or Merck for these can be completely ignored in my opinion. If you google around and ask Chinese chemical producers, you...