Parkinson's Disease Tulip


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Old 08-09-2016, 06:50 PM #1
johnt johnt is offline
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Default Is any levodopa produced in the gut?

The work by Dobb's et al. [1] showing an apparent association between taking laxatives and slower progression of PD has been discussed on this forum [2, 3].

The laxatives used were of different types. So, it seems to me unlikely that they can each slow progression directly. One way to explain the results might be to argue that their action is indirect: laxatives reduce constipation and constipation reduces the efficiency of the absorption of exogenous levodopa in the upper intestine. But, as schwad01 has pointed out, the result appears to apply also to PwP not taking levodopa. We could square the circle if there is an endogenous source of levodopa in the gut.

I can't find any references to the production of levodopa in the gut. However, we do know that the biotransformation through fermentation of tyrosine into levodopa is possible [4]. We do know that the gut houses a vast and on-going chemical experiment. We suspect that people with PD have a different microbiota.

To test the endogenous levodopa hypothesis would be simple: is there any levodopa in the faeces of people not taking levodopa?

A potential therapeutic route is to proactively try to produce levodopa in the gut.

References:

[1] "Quantifying rigidity of Parkinson’s disease in relation to laxative treatment: a service evaluation"
Aisha D. Augustin, André Charlett, Clive Weller, Sylvia M. Dobbs,DavidTaylor,IngvarBjarnas and R. John Dobbs
Br J Clin Pharmacol (2016)
Quantifying rigidity of Parkinson's disease in relation to laxative treatment: a service evaluation - Augustin - 2016 - British Journal of Clinical Pharmacology - Wiley Online Library

[2] Who would have thunk it!

[3] Please read!!!!!!!maybe the first drug to be disease-modifying in pd--please read

[4] International Journal of Scientific and Research Publications, Volume 2, Issue 5, May 2012 1, ISSN 2250-3153
"Biotransformation of a single amino-acid L-tyrosine into a bioactive molecule L-DOPA"
http://citeseerx.ist.psu.edu/viewdoc...=rep1&type=pdf

John
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Last edited by johnt; 08-10-2016 at 07:27 AM. Reason: Fixed link to ref 4.
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Old 08-10-2016, 03:58 AM #2
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Originally Posted by johnt View Post
The work by Dobb's et al. [1] showing an apparent association between taking laxatives and slower progression of PD has been discussed on this forum [2, 3].

The laxatives used were of different types. So, it seems to me unlikely that they can each slow progression directly. One way to explain the results might be to argue that their action is indirect: laxatives reduce constipation and constipation reduces the efficiency of the absorption of exogenous levodopa in the upper intestine. But, as schwad01 has pointed out, the result appears to apply also to PwP not taking levodopa. We could square the circle if there is an endogenous source of levodopa in the gut.

I can't find any references to the production of levodopa in the gut. However, we do know that the biotransformation through fermentation of tyrosine into levodopa is possible [4]. We do know that the gut houses a vast and on-going chemical experiment. We suspect that people with PD have a different microbiota.

To test the endogenous levodopa hypothesis would be simple: is there any levodopa in the faeces of people not taking levodopa?

A potential therapeutic route is to proactively try to produce levodopa in the gut.

References:

[1] "Quantifying rigidity of Parkinson’s disease in relation to laxative treatment: a service evaluation"
Aisha D. Augustin, André Charlett, Clive Weller, Sylvia M. Dobbs,DavidTaylor,IngvarBjarnas and R. John Dobbs
Br J Clin Pharmacol (2016)
http://onlinelibrary.wiley.com/doi/1...bcp.12967/epdf

[2] Who would have thunk it!

[3] Please read!!!!!!!maybe the first drug to be disease-modifying in pd--please read

[4] International Journal of Scientific and Research Publications, Volume 2, Issue 5, May 2012 1, ISSN 2250-3153
"Biotransformation of a single amino-acid L-tyrosine into a bioactive molecule a bioactive molecule L-DOPA"
Apache Tomcat/7..35 - Error report

John
Another thing that I'm wondering about is the subjects not taking L.dopa,
Is this, as seems likely because they're still in the early honeymoon period and
therefore taking agonists. If they are then gut motility will still be a factor, especially if the agonist is a continuous release formula.
It was pre- levadopa that I noticed how my constipation was somehow linked to how well my symptoms are controlled.
This doesn't of course shed any more light on the matter except to suggest perhaps that 'gut/med/absorbtion shouldn't be ruled out because of some subjects not taking l.dopa.

It intrigues me also that the main benefit seems to be for the relief of rigidity and not tremor. Whilst looking into citicholine I came across a paper (only one though) that suggested this compound acted on the striatum rather than the sub. nigra and that the main improvement in the small scale trial was in gait improvement which of course needs rigidity to be controlled.

One thing is certain, if you've lived in Parkinsonia for a while you'll have noticed that whatever the reason the gut is involved somehow.

Thanks for your trouble and insight John.
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Old 08-10-2016, 08:59 AM #3
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if any were produced it would have to be a tiny amount, maybe produced by "microflora"? when you don't get dyskinesias after eating a lot of protein or surge of dopamine and when you don't develop pd like symptoms when fasting for a week one might think the amount of dopamine getting to the parts of the brain where it is needed is very tightly controlled. and think about how little dopamine one really needs on a daily basis when 24mg of requip can control symptoms for a day. and not all of that gets into the right spot in the brain.

Last edited by soccertese; 08-10-2016 at 02:27 PM.
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Old 08-10-2016, 09:23 AM #4
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Lightbulb

Dopamine is manufactured and used in the body in several tissues.

It does not cross the BBB as dopamine and has to be injected for medical use (mostly cardiac treatments).

Dopamine - Wikipedia, the free encyclopedia
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Old 08-10-2016, 09:31 AM #5
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Dopamine is manufactured and used in the body in several tissues.

It does not cross the BBB as dopamine and has to be injected for medical use (mostly cardiac treatments).

Dopamine - Wikipedia, the free encyclopedia
fwiw, l-dopa crosses the BBB

early human and pig transplants of dopamine producing cells, one adrenal glands and one cadaver retinas - i think peggy had this procedure - have been tried and stopped. one product was called spheramine.
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Old 08-10-2016, 10:18 AM #6
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fwiw, l-dopa crosses the BBB

early human and pig transplants of dopamine producing cells, one adrenal glands and one cadaver retinas - i think peggy had this procedure - have been tried and stopped. one product was called spheramine.
I am not sure about this, but Im going to throw it i here anyway..I recall her saying that the transplant came from eye cells?

There was a man from Newport RI who had the pig stem cell transplant..His name was James Finn..I went to the same support group that Jim attended, so he was a friend of mine
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Old 08-10-2016, 10:48 AM #7
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Lightbulb

Yes, l-dopa is a precursor to dopamine production. L-dopa therefore has to cross the BBB.

It is important to understand the difference between l-dopa and dopamine.

Please read the Wiki article I linked, which explains this.
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