Gut bugs could determine individualised therapies

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Related tags: Pharmacology, Roche

The success of personalised healthcare depends on a better
understanding of how gut microbes interact with different
medicines, according to scientists, who believe that the microflora
makeup of an individual has been overlooked when compared to the
area of pharmacogenomics.

Scientists from AstraZeneca in conjunction with Imperial College London,​ think that gut microbes, which influence both the biochemistry and immune system of the host, could play a key role in modulating how medicines can affect the body.

As the community of microbes varies greatly between individuals this could have important implications for the development of personalised treatments, and for drug discovery.

"The discovery that these gut microbes play such an important role means we could have made the first step towards providing patients with personalised, tailored healthcare and medical solutions,"​ said Professor Jeremy Nicholson, one of the authors of the paper.

The team have summarised the scientific evidence showing that gut microbes have a large number of interactions with the body, and that changes to their composition could have significant effects, both good and bad, on an individual.

They believe the exact composition of these microbes in the gut may lead to variations in the effectiveness of drugs between individuals and populations.

Many industry analysts believe the emergence of personalised therapy will become the biggest thing to hit the pharmaceutical industry, changing the way treatments are administered and managed.

In the future it may be possible for doctors to provide a personalised treatment for virtually any illness through the analysis of a blood sample. Similarly, doctors could also spot potential illnesses before they become a problem and take preventative measures.

The Pharmaceutical Research and Manufacturers Association of America estimates that about $100 million (€77 million) are wasted every year in the US alone because patients take drugs that are ineffective or have serious side effects.

"This growing realisation that the gut microflora may have effects that cannot be predicted from the patients genome alone adds an extra layer of complexity to the way in which we carry out drug discovery,"​ said Professor Ian Wilson, from AstraZeneca,​ co-author of the paper.

"At the moment, when developing a new drug we take very little account of factors such as the microflora and this may need to change,"​ he added.

One of the major pharmaceutical companies that have made headway in an effort to introduce personalised medicine is Roche. In breast cancer, particularly one aggressive form of the disease, extremely high concentrations of an abnormal form of the growth factor Her2 are found in the malignant cells.

Together with its subsidiary Genentech, Roche has produced a genetically engineered drug (monoclonal antibody) to block the action of this growth factor. This means if this abnormality is identified before treatment, the patient can be given more specific, personalised treatment.

Roche's product MabThera/Rituxan, which has been used to treat leukaemia for some time now and for a percentage of rheumatoid arthritis sufferers, MabThera/Rituxan is something akin to a "wonder drug".

Roche introduced the first DNA chip (AmpliChip CYP450), which as the first DNA chip test in the world to receive regulatory approval, represented a pioneering new discovery. This test can be used to show whether people metabolise a drug faster or more slowly as a result of their genetic make-up.

The chip provides information that can aid the selection and dosage of a range of medications (for example, anti-depressants,psychopharmaceuticals, painkillers and drugs to treat cardiovascular disease).

Estimates indicate that systematic use of the AmpliChip test before treatment could improve overall efficacy by 10-20 per cent and avoid 10-15 per cent of all serious side effects.

The article, entitled "Gut microbes, mammalian metabolism and personalised healthcare," is published in >Nature Reviews Microbiology​ (advanced online publication 8 April).

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