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March20 podcast Dr Hazen
anti-TMA pill in a year or 2 ? (scroll 12 mins)

Additional info: https://youtu.be/811v7RLXP9M
MEBO Karen
at UK Findacure conf 2020

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MEBO TMAU TESTING DISCONTINUED
(2012-2017)

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Full details : https://goo.gl/TMw8xu
want listed ? contact info@meboresearch.org

MEBO - UBIOME study 2018

'PRESS RELEASE'

NCT03582826
ClinicalTrials.gov

MEBO Gut Microbiome Study
"Microbial Basis of Systemic Malodor and PATM Conditions (PATM)"
Funded by uBiome Research Grant

"Microbial Basis of Systemic Malodor and PATM Conditions (PATM)"

Dynamics of the Gut Microbiota in
Idiopathic Malodor Production
& PATM

Started May 2018 - Ongoing

Current people sent kits : 100/100
3 kits per person

NO LONGER RECRUITING

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TMAU UK ends 23/01/20
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TMAU (Dominican)
Metabolomic Profiling Study
NCT02683876

Start : Aug 2016
Stage 1 : 27 Canadian volunteers to test
Latest click here (26 oct) :
17 samples returned


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MEBO survey for Dr Hazen click here
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Regular readers will know that Dr Stan Hazen et al at Cleveland Clinic are developing a TMA-blocker pill, as they proposed in a 2011 paper that TMAO is a factor in CVD. Recently Dr Hazen and colleagues contacted MEBO as they have always thought they could also help with TMAU. This survey is to give them an idea of the 'state of the community'. It is a "version 1". They may not even look (though they have access permission), but it could be useful to give them an overview of the community

MEBO had a zoom call with Dr Hazen and his team in October. Another zoom call is planned when they have time

MEBO Research Clinical Trials

Tuesday, August 25, 2020

new TMA-inhibitor ... based on Histadine ?

A new paper presents a new Trimethylamine-inhibitor.

They call 'compound 5' ? 
Seems to be based on a Histadine Compound ?

authors :
The 'physical' work in the paper seems to be done by a Stanford Academic of chemical structure ?
The' theory' by an Academic researcher based in a Spanish Uni.

Discovery of a histidine-based scaffold as an inhibitor of gut microbial choline trimethylamine-lyase

Full paper is pay access

Moustafa Gabr 1, Katarzyna Świderek 2
Affiliations
1 Stanford University, Radiology, 300 Pasteur Drive, 94305, stanford, UNITED STATES.
2 Universitat Jaume I, Department de Quimica Fisica i Analitica, SPAIN.

Abstract

Anaerobic choline metabolism by human gut microbiota to produce trimethylamine (TMA) has recently evolved as a potential therapeutic target because of its association with chronic kidney disease and increased cardiovascular risks. Limited examples of choline analogs have been reported as inhibitors of bacterial enzyme choline TMA-lyase (CutC), a key enzyme regulating choline anaerobic metabolism. We utilized a new workflow to discover CutC inhibitors based on focused screening of a diversified library of small molecules for intestinal metabolic stability followed by in vitro CutC inhibitory assay. This workflow identified a histidine-based scaffold, (compound 5), as a CutC inhibitor with an IC50 value of 1.9 ± 0.2 μM. Remarkably, compound 5 was able to reduce the production of TMA in whole cell assays using various bacterial strains as well as in complex gut microbiota environment. The improved efficiency of the new scaffold identified in this study in comparison to previously reported CutC inhibitors would enable optimization of potential leads for in vivo screening and clinical translation. Finally, docking studies and molecular dynamic simulations were used to predict putative interactions created between inhibitor and CutC.



Uneducated skim-read thoughts on the paper

TMA-inhibitors would probably have been around decades ago if anyone looked. They look for choline analogs ? Probably simple too. 
No-one looked until around 2011 (still waiting for product to reach market).
This seems to be the 3rd known TMA-inhibitor research ? (others ... Hazen-P&G, Balskus lab?)
Balskus lab don't seem to be bringing a product to market ?

On this paper :
This paper has a good vibe as it seems simple process. A theorist and a practitionist.
Probably took pretty quick to do.
Also looks like 1 compound.
It's unknown if that is their research over or if they will continue and maybe create a product.   

The reason for the paper will be all the talk about TMAO possibly being inplicated in CVD and kidney disease etc.      

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6 comments:

Anonymous said...

Hmmm....I know some people at Stanford. Maybe we could create a little awareness in this department.

Aug 25, 2020, 6:36:00 PM
Anonymous said...

We still waiting for proctor and gamble to bring their product to market, they lied about the time it will come, so at this point, I will find my own cure, or what works for me, they been messing around with this for years, and still nothing....go digure

Aug 27, 2020, 11:04:00 AM
Anonymous said...

What would happen if one took a small tablet of histidine supplement just before eating a high -choline food?
Would there be any effect, or is the chemical process more complicated?

There are several histidine supplements on the market. I wish a doctor already familiar with TMAU problems could advise us on how to use this information with products already available, so we wouldn't have to hope the researchers might develop a new product especially for TMAU.

Sep 1, 2020, 8:31:00 PM
Anonymous said...

to the person who said you know people at Stanford. I agree create a little awareness if you can. What department can we talk with?

Sep 7, 2020, 1:38:00 AM
Anonymous said...

If you look up Moustafa Gabr on Google, you find that he is connected with the Radiology Department at Stanford. I don't know how one goes about this properly. Perhaps an organization like NORD, or a representative of MEBO could write a letter just to let them know that the problem of TMAU exists and that we are following this line of research with great interest, etc.

It would seem that there wouldn't even be a need for a new product if we only knew how to take available histidine supplements (of which there are many) in such a way as to affect TMAU. Who could we ask?

Sep 10, 2020, 5:06:00 AM
Anonymous said...

Looking up "histidine compound 5" on Google, I find that it is a compound that includes iodine and nitrogen, in addition to histamine.

At least I think that's what it means!

So...what if one took a little histidine tablet, a little iodine (kelp) and a little nitrogen, all together? Would this be roughly equivalent to Compound 5?

Over the years, cysteine, iodine and nitric oxide have been mentioned as helping with TMAU. L-arginine and l-ornithine are very effective. Dr. Weil has a supplement that increases blood flow with the use of nitric oxide. So, this is the general area. Now, we just need something specific to try.

Sep 17, 2020, 11:38:00 PM
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