How to Make Your Own NHPN-1010 (Hough Ear Institute's Bomb Blast Pill)?

[UHPTS]

Hi.

In the latest podcast with Hough Ear Institute they talk about "bomb blast pill". This drug is supposed to be able to regenerate nerve endings in cochlea possibly helping getting rid of tinnitus.

The drug name is NHPN-1010 and if everything goes right it will get on the market in mid 2020s.

Now I found that this drug consists of HPN-07 and N-acetylcysteine (NAC). NAC is available from online shops but HPN-07 I only found here:

https://www.sigmaaldrich.com/catalog/product/sigma/sml2163

...seems like some drug company which makes various chemicals for use of drug makers (???).

Anyway looks like it is possible to buy HPN-07 from them. Do you think that taking, let's say 1mg of HPN-07 + some volume of NAC will at worst just have no effect?

Thanks for your thoughts!

 

[ajc]

Anyway looks like it is possible to buy HPN-07 from them.

It's not. Sigma-Aldrich only sells to pharmaceutical companies, laboratories, etc.

 

[Joly]

How do you know Hough Ear Institute's pill will be released in mid-2020? They are in the testing phase.

 

[Lucifer]

How do you know Hough Ear Institute's pill will be released in mid-2020? They are in the testing phase.

That was an estimate by Hough Ear Institute. Mid 2020s can be between 2023-2026. Hopefully if they receive fast track status then it can come out sooner.

 

[Rb86]

Well, that would either work and "yay" or, it wouldn't and is it the right dose? Is it actually what their pill is? Does their pill work at all to begin with?

So many variables.

 

[Joly]

Do you think that hearing regeneration treatments could help against hyperacusis?

 

[UHPTS]

Do you think that hearing regeneration treatments could help against hyperacusis?

I didn't notice any mention about hyperacusis in this podcast so I would say no. But then we do not know what drives hyperacusion so maybe if the nerves regenerate it can have positive effect on hyperacusis as well.

 

[UHPTS]

Well, that would either work and "yay" or, it wouldn't and is it the right dose? Is it actually what their pill is? Does their pill work at all to begin with?

So many variables.

I would recommend you to listen to the podcast interview as in my humble opinion there are only a few podcasts on tinnitus that are worth listening to. This is one of them. There's one thing that strikes me though. The doctor is talking about the pill and he also has tinnitus. If I were him I would try the pill myself, after all the pill has already passed safety tests so nothing to worry about.

I found out that the dosage they administered to the patients was 1.5g. Given that 5mg costs around 50EUR... well not even worth counting what it would cost to take it daily for 2 weeks.

 

[FGG]

@UHPTS

Where did you get that dosage?

 

[UHPTS]

@UHPTS

Where did you get that dosage?

Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC

 

[ajc]

I found out that the dosage they administered to the patients was 1.5g. Given that 5mg costs around 50EUR... well not even worth counting what it would cost to take it daily for 2 weeks.

€210,000 EUR for two week treatment.

Price of a good house.

 

[UHPTS]

Wish there was some chemist here who could tell how hard is it to synthetize this molecule.

 

[linearb]

Assuming you went to the effort of setting up some kind of LLC that Sigma would do business with, even if the Hough pill is literally just NAC mixed with this stuff, this seems likely to be wildly financially unfeasable.

I don't know, at all, what doses of HPN-07 Hough is using, but the information right on Sigma's page indicates that in rats neuroprotective effects are seen at 75 mg/kg/day in drinking water. For a 75kg male, that's a little over five grams a day, which would cost $42,000 a day; even if we assume the drug might be 100x as potent in humans as rats, that's still obscenely expensive.

I would assume Chinese laboratories would synthesize this much cheaper, and if you have access to IR spectrometer and GC/MS to validate the results that might or might not get you a product on par with Sigma's (unlikely to be as pure) -- but then at that point you're messing around with a drug known to have neurogenic effects, with a dose profile we don't really know, and very very little in the way of published data.

My view is that most things which can positively impact tinnitus can also negatively impact it, because you're tinkering with the neurological and chemical basis for the condition. Messing around with DIY bimodal stimulation seems reasonably safe to me because the effects are believed to be time-limited; messing around with things that might cause new neurons to form seems questionable simply because if you push things too far or in the wrong direction I am not sure how you'd undo that.

If you manage to figure it all out though, good luck and let us know what happens!

 

[UHPTS]

For a 75kg male, that's a little over five grams a day, which would cost $42,000 a day; even if we assume the drug might be 100x as potent in humans as rats, that's still obscenely expensive.

How is it that you know my weight? I think I can go down 10kg if I stop taking Mirtazapine.

But on a serious note, I believe that the price will go dramatically down when they start making high amounts of this drug.

What I don't understand is why if this drug was already tried in 3rd level of FDA trials (didn't make it through though as it wasn't effective on whatever they were testing it for), it is obviously safe, why it has to go through the same cycle for cochlea nerve regeneration.

It's scary to see that claims for treatments of tinnitus that are being made these days were already made in 2014. I'm probably wrong but I suspect that for some scientists this is good grant money. If they finish their research, funds stop. How is it that Elon Musk starts Neurolink and 2 years later there is new incredible tech beyond anything that existed so far while other scientists can't get a simple device working in 25 years?

 

[Bobby B]

If this drug only regenerates nerve endings, this won't cure tinnitus when it is caused by hair cells damage, such as noise damage.

It may help speed up recovery from hyperacusis though. I believe nerves can heal themselves, at least to a certain degree but it is very very slow, takes years.

It took 4 years for my hyperacusis to heal to pre-trauma level, so surely something must have been healed.

Not the tinnitus though. Tinnitus is also getting a bit better but that's happening even slower.

 

[spacehunter]

€210,000 EUR for two week treatment.

Price of a good house.

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 usually get prices that are at least a factor 10 cheaper. Just out of curiosity I wrote yesterday a few Chinese labs and already have gotten an answer for HPN-07 ($4650 for 25g, $8000 for 50g, 98%> purity). So provided, that a purity of >98% is safe enough for medical use it is still very expensive but not even close to the price of a house. For Ebselen I found websites, which offer 50g of 99.3% pure Ebselen for about $4000.

I am not saying that this will be the final price of the treatment - maybe one needs even higher purity (say 99.9%) for medical use, but in any case the prices often mentioned here are not valid at all (especially since they only refer to very small amounts with a purity only certified to be larger than 98%).

What concerns me more is that there is no definite answer on the dosing. As mentioned in the Hough Ear Institute's Hair Cell Regeneration Project thread in Research News there is no clear answer about the right doses for taking the drug. Clinical trials suggest no more than 1.5 grams per day, the patents suggest in some parts 20 grams for humans, in the case example for chronic hearing loss they even talk about 0.3g/kg twice a day for 14 days - no less than 48 grams a day for 14 days.

In my opinion the biggest problems of doing the Hough Ear Institute drug by oneself is, that we do not know at all the right doses (a too low dose might not do anything other than burning money, a too high dose for intake might have very adverse health implications) and that it is unknown, what the impurities will cause (maybe the remaining 2% are very poisonous molecules, which will be especially harmful for high doses).

 

[Bill Arsenault]

 

[spacehunter]

Wish there was some chemist here who could tell how hard is it to synthetize this molecule.

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 for it as many intermediate products are poisonous and also volatile. This is also the problem when making it - you want to be 100% sure not to have any methanol left...