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

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MEBO Karen
at UK Findacure conf 2020

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MEBO Map Testing & Meetups

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MEBO - UBIOME study 2018



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

Started May 2018 - Ongoing

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


Participation info : LINK English

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BO Sufferers Podcasts



TMAU Petition world
TMAU UK end total:262
TMAU UK ends 23/01/20
TMAU Petition USA end total 204
USA : Moveon open
TMAU (Dominican)
Metabolomic Profiling Study

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

Note : Stage 1 is Canada only.
Return cut-off date : passed
Analysis can take 6/8 weeks
Analysis start in/before Nov
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Denver TMAU Test Lab survey click here
click to Read more/less

USA survey for anyone who wants to improve Denver TMAU test

begun : Dec22
end : no ending for now

A trainee genetic counselor is working at the Denver TMAU test lab. Probably as part of her training. As a project she wishes feedback on any aspect of the Denver TMAU test and process. You can fill in the survey and/or email her (email address is in survey). It's meant for USA people, but perhaps others can give their view too (as we have so few opportunities).

quote from her rareconnect post

"Hello all! I wanted to make you aware of a research study being conducted to better understand the experience and needs of individuals with trimethylaminuria with a goal of being able to create improved patient and healthcare provider education materials. Any participation is completely voluntary and all responses remain confidential. Feel free to use the contact information within the link with any questions or share the survey with others with TMAU."

see this post for more details

Thursday, October 31, 2019

Gene Editing and FMO3 : cure in 5-10-15 years ?

Ultimately, the cure for FMO3 Genetic Malodor (e.g. TMAU1) will be Gene Therapy.
The question is, when ?
Probably sooner than expected.

Gene therapy is where they can correct errors in the code.
A bit like word-processor correcting, or correcting with copy and paste.

There are various gene-editors, but the 'big game-changer one' seems to be CRISPR ... first published about in 2012.
Last week a new paper was published that spoke of an improvement which makes 'single letter' correcting of DNA safer and easier.
Most people with FMO3 flaws will have 'single letter' (base) flaws.

Prof Jennifer Doudna, the co-founder of CRISPR said in 2015 :
She expects clinical therapies within 10 years (so 2025 ?)
Current obstacles with gene-editing to overcome :
Probably safety, precision, worry about side effects ?, delivery to the body, cost, no human trials yet etc

CRISPR is cheap to do in a test tube, but delivery to the body, licencing cost etc will be dear to start with probably. 

FMO3 most common types of gene flaws.
Most with 'sub-par' FMO3 (either always, or transiently), will be due to NUCLEOTIDE MISSENSE  errors.
This is to do with A,G,T,C.
FMO3 protein is a 532 amino acid sequence.
The DNA will be 3 nucleotides on each side to make up the amino acid (532x3x2 letter code).
Like AA AG TC etc.
Most FMO3 people will have one of those letters wrong, making the amino acid incorrect at that codon (532 rung ladder of codons).
Examples : E308G E158K  V257M
These 3 mistakes are common, but most FMO3 people seem to carry 2 of the mistakes (either at same codon, or as a mix)

So these flaws should technically be easy to fix when the technology is ready (?)
They say the easiest type to fix are :
single gene : tick ... FMO3
single base flaws  : ... most FMO3 people have these

Has FMO3 ever been tried in CRISPR ?
It seems a Chinese lab experimented with mice in 2015 re FMO3.
Probably proving the principle for FMO3.
Chinese paper 2015 FMO3 knock-in/knock-out in mice. 
No follow up seemed to happen.
Probably as FMO3 is regarded as not an important gene, and 'sufferers' are rare (an incorrect assumption).

Where would FMO3 treated cells be delivered to the body ?
Probably the liver.
FMO3 is in a lot of places in the body, but mainly in the liver.
Sickle-cell anemia is being looked at now for CRISPR treatment, as they can take blood out and treat it. But they have to put it back in the bone marrow.
No human clinical trials have been completed yet.

Dr David Lui paper from Oct 2019 
Dr Lui of Harvard seems to have improved the CRISPR targeting for base mistakes (? base editing)
It has been tweeted by peers, so seems a breakthrough.
new gene-editing technique may be capable of fixing almost all disease-causing genetic defects 

So, whatever happens re FMO3 smells and/or TMAU, keep in mind the genetic type may be close to being genetically cured in 5-10-15 years (or sooner ... as many gene disorders will be).

Notable People to search in Gene-Editing and CRISPR world (from skim-reading about CRISPR)
Prof Jennifer Doudna (oct19 article)
Prof Emmanuelle Charpentier
Prof Feng Zhang
Prof George Church
Dr David Lui
... many more.

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