Dose Equivalence Question - Trehalose Nas... - Cure Parkinson's

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Dose Equivalence Question - Trehalose Nasal Spray

Router_ profile image
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academic.oup.com/braincomms...

Hey there - came across this one on my usual search and found it quite compelling.

2% Trehalose - nose spray, pretty easy to prepare for oneself.

I find different number depending on logic for dose equivalent, roughly x 12 for mouse / 70kg equivalent human, which would be roughly 24g on 100g saline if I am not mistaken. Then making sure the nose spray delivers approximately 10ul per pump.

Does that make sense ?

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park_bear profile image
park_bear

To find human dosage per kilogram divide mouse dosage per kilogram by 12

Router_ profile image
Router_ in reply topark_bear

As in 2% / 12 * 80 = 13% ?

Well now I have a 19gr solution :D Will try and see how it goes

park_bear profile image
park_bear in reply toRouter_

Okay this is a really interesting study. Oral trehalose does not work because it is broken down into glucose in the intestine. Ways that have been tried to get around that are a massive oral dose of trehalose, which is bad because it loads the body with glucose, or IV trehalose, which is not exactly convenient for home use. So, intranasal is really interesting. I'm going to have to review the details of the study before I get back to you further on dosage.

Router_ profile image
Router_ in reply topark_bear

thank you

park_bear profile image
park_bear in reply toRouter_

Fascinating. This study says that it is the soluble oligomers of alpha synuclein that cause the trouble and that the insoluble aggregates do not. Moreover, that Lewy bodies are actually protective and remove the troublesome version from solution.

What is problematic here is that only the mice that received both oral and intranasal trehalose received benefit, and that either route alone was insufficient. Oral trehalose in humans is unlikely to be effective due to the conversion to glucose in the gut. According to this paper the same is true for mice so why that should help with efficacy is unclear. Also, “There are potential limitations to trehalose treatment in different species, as in rodents, 50% of the surface area of the nasal cavity is covered by the olfactory epithelium, compared with 8% in humans.” This may require increasing the human dosage above that calculated below.

Some unanticipated downside is always possible. If a person is willing to take that risk, this could work, which would be a huge benefit.

The mice underwent intranasal administration every week (eight times for 60 days): a total of 10 μL of 2%(w/v) trehalose in phosphate buffered saline into the nasal cavity. 2%(w/v) would be 20 G trehalose per liter of solution.

Mouse weight about 42 G . See here for detail: Tanji K, Miki Y, Mori F, et al. A mouse model of adult-onset multiple system atrophy. Neurobiol Dis. 2019;127:339-349

To convert to a 70 kg human we have: 70000/(42*12) = 140, the multiplication factor for the dosage. 10 μL of 2% trehalose x 140 = 1.4 mL of 2% trehalose, weekly, or, .2 ml daily, dripped into the nose. .2 ml Is a pretty tiny volume. So maybe applying more on a daily basis would be in order, given the lesser exposure of the olfactory epithelium in humans.

Phosphate-buffered saline (PBS): You can buy phosphate buffered saline at Amazon, either as a prepared liquid or as powder to be dissolved in water. You can make your own unbuffered saline by adding 9 G of salt to 1 L of water.

I would recommend sterilizing before use. 20 minutes in a pressure cooker at 15 lb pressure should do it.

Router_ profile image
Router_ in reply topark_bear

Wouldn’t the other option be to simply increase the percentage of trehalose in the solution ?

I think the nose cannot easily absorb a lot of fluid, it usually ends up in your throat which would end up in the digestive route.

I have prepared my spray using distilled water and salt. Added 19g of trehalose which was well absorbed by 100ml of saline it seemed.

now I got to do the math what that means in terms of daily dosing. My dose is roughly factor 10 of 2%. To get to 1,4ml equivalent of 2% that would be 15 applications within the week.

Now obvious question wether one time high dose is the equivalent to 15 individual doses 😄

park_bear profile image
park_bear in reply toRouter_

Yes you can increase the concentration. Whatever works best for you is good.

Router_ profile image
Router_ in reply topark_bear

Thank you, also something to consider the amount ejected by your nasal spray, tested mine and came out consistently between 0.08-0.1 ml, which is already 10x dosing.

So my spray is actually already pretty close, not taking into account your comment regarding surface area differences of olfactory epithelium.

Might try to find something on dose equivalent studies eg on nasal ketamine that could give a hint

Boscoejean profile image
Boscoejean

cphi-online.com/nasal-spray...

park_bear profile image
park_bear in reply toBoscoejean

They're looking for a partner to market and sell the product.

If anyone here is feeling entrepreneurial here's a chance ;-)

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