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Friday, February 4, 2011

New TMAU review paper by Dr Christodoulou

Trimethylaminuria papers published in medical journals are a rare occurrence. So it is nice to see a paper published recently, although it is only a review rather than new research. The review is by Dr John Christodoulou of the Genetic Metabolic Disorders Service, The Children's Hospital at Westmead and Disciplines of Paediatrics and Child Health and Genetic Medicine, Sydney Medical School, University of Sydney, Sydney, Australia.

Dr Christodoulou has a history in trimethylaminuria research. Indeed He authored the research proposal which was meticulously written that gave the community hope a couple of years ago, which was posted in the blog. Unfortunately funding did not materialize for the proposal.

Here is the pubmed information for Dr Christodoulou's new TMAU review paper below :

Trimethylaminuria: An under-recognised and socially debilitating metabolic disorder.
Christodoulou J.

Abstract
Primary flavin mono-oxygenase 3 deficiency, an inborn error of choline metabolism, leads to an accumulation of trimethylamine, which because of its associated pungent odour of rotting fish, is a socially crippling disorder. Although it often has its onset in early childhood, it may take years or even decades before the diagnosis is established. In this review the clinical biochemical and genetic features of the disorder are reported. The principles of therapy will also be covered, including dietary, pharmacological approaches, as well as techniques used to manipulate the gastrointestinal environment as a strategy to reduce the gastrointestinal load of trimethylamine.

Dr Christodoulou abstract of TMAU review 2011

Dr Christodoulou, being a geneticist and pediatrician, is interested in all genetic disorders. Currently he is working on research for phenylketonuria that involves introducing a genetically engineered probiotic to the gut that is rich in the enzyme that metabolizes the compound present in the gut that PKU sufferers cannot metabolize. This idea has been suggested for TMAU too, and in principle may work for TMAU also, metabolizing the trimethylamine present in the gut.

At present, John and his team are also investigating genetically engineered probiotics as a treatment of human disease. One such disease, Phenylketonuria (PKU), is due to phenylalanine hydroxylase deficiency and, if untreated, results in profound intellectual disability, seizures and aggressive behaviour. Treatment consists of a life-long diet, restricting phenylalanine intake. The diet, however, is unpalatable, and for a number of reasons, compliance tends to deteriorate with age. A group led by John, in collaboration with Dr Ian Alexander of the Gene Therapy Research Unit, Dr Ted O’Loughlin of the Gastroenterology Research Unit (both at the Children’s Hospital at Westmead), and Professor Peter Pouwells of the TNO Nutrition and Food Research Institute in the Netherlands, is developing a novel therapy for treating PKU. This will involve genetically engineering harmless Lactobacillus bacteria to produce an alternate phenylalanine-metabolising enzyme, phenylalanine ammonia-lyase. These engineered organisms, if given orally (as a ‘Yakhult’ type preparation), should metabolise phenylalanine in the small intestine, preventing blood levels from rising. If successful, this novel form of treatment could be translated to other human diseases

Source : Dr John Christodoulou career biography

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