Researchers Find Gene Network That Repairs Central Nervous System

[Twitch]

LOS ANGELES, Feb. 19 (UPI) -- Researchers identified the genetic mechanism that promotes repair of the peripheral nervous system, as well as a drug that promotes nerve regeneration in the central nervous system, according to a newly published study.

Scientists at the University of California Los Angeles gained the new understanding of the nervous system by mapping the action of messenger RNA, or mRNA, in the nervous system, and they think the finding could lead to better methods of treating injuries.

Nerve cells transmit and receive electrical messages to cells and tissue in organ systems. While some nerve cells recover after being damaged in an injury, such as those in the peripheral nervous system, other generally cannot recover at all, such as those in the central nervous system.

Having discovered how mRNA helps certain nerves repair themselves, as well as the effects of the drug Ambroxol on the central nervous system, the UCLA researchers see better injury treatment down the road.

Full article
Neuron journal - would be nice if someone could get full text
Ambroxol (available OTC, used to treat sore throat, respiratory diseases)

 

[Cheza]

@attheedgeofscience Requesting your input on how this development relates to treatment of tinnitus. I did some very cursory research of the relationship between the peripheral nervous system and tinnitus and really couldn't find anything definitive.

Perhaps this is just a step in the right direction towards repairing nerves in the CNS ...?

 

[Nucleo]

It'd be nice to know if tinnitus originates in the CNS or in the PNS. Or both. Also possibly different based on the etiology. I do think this question is still up for debate.

 

[Reinier]

"Scientists at the University of California Los Angeles gained the new understanding of the nervous system by mapping the action of messenger RNA, or mRNA, in the nervous system, and they think the finding could lead to better methods of treating injuries."
End quote.

Is this not exactly the same as scientists at Stanford are doing with the hair cell regeneration? Mapping which genes are promoting hair cell regeneration in chickens and which genes prevent regeneration in ears of mammals.

 

[generalfuzz]

Interesting. Ambroxol has been thought of for treating tinnitus:

http://www.google.com/patents/CA2532304A1?cl=en

 

[beeeep]

Time to try another drug?

Interesting. Ambroxol has been thought of for treating tinnitus:

http://www.google.com/patents/CA2532304A1?cl=en

Interesting side node:
While googling this stuff, I came across the following post on a German forum:
https://www.tinnitus.de/showthread.php?4610-Mucosolvan-Hustensaft

A rough(!) translation of the first post:

In the last two years I twice had a cough, and both time I had the feeling that the cough syrup Mucosolvan (Ambroxol) lowered my tinnitus considerably. Maybe I'm just imaging things (One can actually imagine quite a lot), but in general there's no fluctuation in my T intensity.

Did someone notice anything similar with Mucosolvan?

I found a patent about it, (but that doesn't mean anything about its effectiveness, there are many patents about all kind of things).

Please don't try it as long as you don't need to take cough syrup anyway.

In a later post he vaguely wrote about the dosage, that he probably took a higher than usual dosage when he noticed the effect:
("Die ersten beiden male (vor jeweils Monaten) als ich mir den TT-Effekt eingebildet hatte, hatte ich vielleicht ein bischen viel erwischt[...]")

He noticed the difference after roughly 30 mins (he didn't expect it to influence his T, he just suddenly realised that it was a really good day).

Someone else tried the normal dosage without any effects.

However, seeing that the patent mentions:

It is also preferred to use ambroxol or one of the pharmacologically acceptable salts thereof as described above, the ambroxol being used in a daily dosage of 30 mg to 4000 mg, preferably 150 mg to 3000 mg, most preferably 350 mg to 2500 mg, most preferably 500 mg to 2000 mg.

I would guess that higher dosage might be useful.

In any case, this stuff seems to be:
a) Over the counter medicine (at least here in Germany).
b) Pretty cheap (there are thousands of syrups or tablets of this kind).
c) Pretty harmless, especially compared to Trobalt and other things.

Maybe we could start our own little tests? I'm not sure if I'd risk it, at the moment I'm somewhat habituating, but still...



The patent itself seem to be bull****. To me it basically reads as "We think this drug might help, so if someone tries it, we already hold a patent on it, including several combinations with other drugs!" I don't think they ever did any trial on this or plan to do any...

 

[beeeep]

One more thing.
I just got hold of the paper.
It seems to be pretty basic research. They did some computational biology (i.e., simulations) to check why central nervous system (CNS) axons don't regrow while those in the peripheral nervous system (PNS) do over time. Seems like they don't send the right chemical signals to start the regrowth process because they don't express the correct genes, while the PNS axons do it. (Well, stupid CNS axons, why can't they get it right?)

They then used more simulations to try and find drugs that might activate those signals in CNS neurons.
Their simulation found the following candidates (i.e., those were identified by the simulation, which doesn't mean anything yet): ambroxol, lasalocid, and disulfiram.
They then did some pretty ugly things with mice, basically damaging their eye nerves and then injecting those drugs into their eyes. After letting them suffer for some days, they killed them and checked their retinal ganglion cell axons (Sounded like a standard procedure to find out about CNS regrowth). Et voila, while lasalocid and disulfiram were useless (actually, injecting them into your eye seems to be a pretty bad idea, according to their statistics. Who would have guessed this), the ambroxol seemed to give a modest increase in recovery.

Ambroxol (Amb 25 mg/ml) or vehicle was injected into the eye just before ON crush. Animals received daily 300 mg/kg ambroxol or vehicle by i.p. injection for the first 5 days after the crush and then they received 150 mg/kg until day 14. At day 7 ambroxol (25 mg/ml) or vehicle was injected into the eye. Tracer CTB was injected into the eye on day 11 and animals were sacrificed on day 14.

We acknowledge that the effects of ambroxol are modest compared with combinatorial genetic manipulations (Sun et al., 2011), which is perhaps not unexpected given the paucity of drugs that enhance regeneration to any extent.

So anyone wanna try injecting large amounts of this stuff into his inner ear? You may of course skip the "sacrificed on day 14" part, if you like...

 

[linearb]

you can buy ambroxol on eBay :-p

 

[mtr]

@beeeep
I'm from Germany too. Thanks for your evaluation of the paper.

What about the following:

Let's combine Ambroxol (liquid) with the procedure of iontophoresis (forwarding to the inner ear via electrical impulses). Then we don't have the side effects experienced by the animals. Iontophoresis with a liquid which contains 4% lidocain is an alternative therapy for tinnitus since the 1980s. (Study from 1985 showed some improvements on 31 of 50 patients, 19 without improvement)
(https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-2007-1008159)

In the 1980s there was no knowledge about the effects of Ambroxol on nerve regeneration and repair.
- Based on the UCLA Research Ambroxol can promote central nervous system repair which is a difference in contrast to Lidocain.
Due to the fact that Ambroxol is 50 times stronger than lidocaine by inhibting pain-sensitive periphal neurons (Source: wikipedia), the dosage should perhaps be much less than the one used for the lidocaine iontophoresis. But this is a question a medician should answer.

Besides the iontophoresis maybe the oral taking of higher doses of Ambroxol (descending) can show improvements (temporary or permanent who knows). For example: 1st Day: 500mg, 2nd: 400mg, 3nd: 300mg ...

 

[attheedgeofscience]

@attheedgeofscience Requesting your input on how this development relates to treatment of tinnitus. I did some very cursory research of the relationship between the peripheral nervous system and tinnitus and really couldn't find anything definitive.

From a tinnitus perspective, I have no opinion as to whether this is "breaking news" or not. Personally, I find too many research posts are shoved into the research section of this forum. I mean, if you were to search the full text (see attachment) - can you find the word "tinnitus" mentioned even once? I couldn't... So there's a clue.

Stuff like this probably falls into the basic research basket. That is discovering something which may - or may not - have practical implications later on. And for all I know, these researchers may just be looking to highlight their not-so-interesting research in order to secure funding for something else. As an example of that, Prof. Rauschecker went on to promote his latest research towards the end of last year:

www.hearingreview.com/2015/09/neuroscientists-identify-brain-mechanism-responsible-tinnitus-chronic-pain

Well... following the release of the article, I was in touch with a few of my sources due to the phrasing of the words in the title which might lead some people to think that there is/was a high degree of novelty within the paper. Trouble is: there isn't...

It is actually pretty easy to present a dichotomy between what matters and what doesn't: follow the money! Pharma companies are the ones who have to convince - to begin with - private investors that their research will provide a return-on-investment. That means that - unlike the average researcher - pharma companies have to do all the hard work: the work that really matters, that is.

So if you - and others want to do yourselves a favour - then keep your eye on these basic topics:

• Auris Medical
• SciFluor Life Sciences
• Otonomy
• The Tinnitus Research Initiative
• Prof. Ernest J. Moore

would be nice if someone could get full text

See attachment.

 

[Twitch]

Thanks for attaching the full text @attheedgeofscience

I was in 2 minds whether to post this under research news for the exact same reason, the research did not mention tinnitus but I felt at the time of posting that repair of the CNS would possibly have an unintended but positive effect on tinnitus if ones tinnitus originated from a disorder of the central nervous system. Is it in the cochlea or brain? Here's an excerpt from this research:

In the last decade, animal research has clearly demonstrated that tinnitus is a pathology of synaptic plasticity (Guitton et al., 2003; Guitton and Dudai, 2007). However, the research done using animal models has also pointed to dual aspects of the biological mechanisms underlying the ontogeny of tinnitus. Indeed, if tinnitus originates into the cochlea, at the level of the synapse between the auditory hair cells and the primary auditory neurons, its perception and long-term maintenance involves complex networks in the central nervous system, both in auditory and in non-auditory (among them limbic) structures. Thus, the biology of tinnitus comprises both molecular and system-level components.

And also a theory excerpt below from @Nucleo

If synapses are damaged then nerve fibers cannot be properly stimulated anymore. Potassium channels remain closed since no electrical stimulation is received.

I wouldn't completely bury this research as beating a dead horse as it does have some potential for us T sufferers.

 

[Cheza]

Well... following the release of the article, I was in touch with a few of my sources due to the phrasing of the words in the title which might lead some people to think that there is/was a high degree of novelty within the paper. Trouble is: there isn't...

Thank you for posting this. I don't have the expertise to address the novelty of the paper, but I certainly found it interesting. The more I delve into this, the more I see research addressing similarities between physical pain, and emotions and tinnitus, and their correlating areas of the brain.

Persistent lack of quality sleep has deleterious affects on the brain, also, which affects the emotions, which can affect tinnitus. It's like being caught in a vicious cycle with no exit door.

 

[beeeep]

Interestingly, there is a trial for Ambroxol as a cure for Parkinson...

https://www.cureparkinsons.org.uk/news/promising-respiratory-drug-focus-of-new-trial-for-pd

 

[linearb]

I got a bunch of Thai ambroxol in the mail today :-p

 

[DebInAustralia]

Which brand linearb?

 

[Silvio Sabo]

I got a bunch of Thai ambroxol in the mail today :-p

It's being sold as medicine for sore throat here in Sweden. The active substance in the thing they have here is abroxolhydrochloride.

 

[linearb]

Which brand linearb?

Mucodic

 

[Cheza]

I got a bunch of Thai ambroxol in the mail today :-p

You bought it for your tinnitus? What dosage are you planning to take? Please keep us updated.

 

[lapidus]

I got a bunch of Thai ambroxol in the mail today :-p

Any effect?

 

[linearb]

Any effect?

haven't really taken it. I have a rather large backlog of such things at this point :-P

 

[Twitch]

I took it in rather large doses of 240mg at once, even 60mg tends to make me really thirsty. Let me know how you get on @linearb

 

[linearb]

I took it in rather large doses of 240mg at once, even 60mg tends to make me really thirsty. Let me know how you get on @linearb

...any effect on your T?

 

[Twitch]

Nope not that I recall

 

[DebInAustralia]

Hey linearb,

did you end up taking the ambroxol?

 

[Beste]

Nope not that I recall

Hi Twitch

Do you continue to take this drug? Is there any difference on your T?

 

[DebInAustralia]

any updates on ambroxal?

 

[Twitch]

Sorry for the late responses guys. My tinnitus has been unmanageable lately and has spiked considerably . When I eventually ordered Ambroxol, it was from Germany and came in a box of 100 or so, I think 60mg. I used to regularly take 240mg which was 4 tablets at a time and as you can imagine, I ran out within no time. I can't say I stuck to a particular regime and also I didn't notice Ambroxol having any noticeable effect on my T. The only noticeable side effect I experienced was tingling of hands/fingers.