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Tuesday, July 15, 2008

Mitchell/Smith TMAU 2001 paper : Their treatment advice both for then and in the future

The diagnosis of 'TMAU' was first recorded around 1970, and over the last 38 years it is unclear if there is much research attention either in TMAU or the enzyme involved, the Flavin Mono-Oxygenase enzymes (of which FMO3 is by far the most abundant and seemingly most important in humans). FMO are perceived as not having a majorly vital role in humans, and the sense is that few researchers are researching TMAU or the FMO enzymes, hence so few research papers have been published on the subject as well.

This is a well-known paper from 2001, written by 2 of the few researchers in the UK, Dr Steven Mitchell and R. L. Smith. For this post, we quote their long-term ideas as to solutions for TMAU, probably the ultimate goal being gene therapy.

It is unclear if gene therapy is possible today for TMAU. For instance, if it's more to do with no perceived need for it in terms of numbers of sufferers or the perceived seriousness of the problem by the medical establishment, or the cost, or practicalities (such as length of the treatment effect or effectiveness).

As to the future, one may envisage some new approach to treating or managing the condition quite apart from the obvious one of gene therapy with replacement of the human gene for FMO3. Alternative approaches might embrace the following: use of gut absorbents, such as charcoal or ion-exchange resins; modify the gut flora to reduce the bacterial species responsible for the conversion of precursors to trimethylamine; incorporate micro-organisms "engineered" with human FMO3 into the gut flora, to oxidize any trimethylamine released to its non-odorous N-oxide; provide riboflavin supplements, a precursor of the FAD cofactor for flavin monooxygenase function, in an attempt to maximize any residual activity; and finally, from the cosmetic point of view, the development of "malodor suppressants" in hygiene products to disguise the offensive smell of trimethylamine.


http://dmd.aspetjournals.org/cgi/content/full/29/4/517#SEC10

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