February 20th 2004 - Financial Times Article by SIMON HADLINGTON

© 2004 The Financial Times Limited. All rights reserved

A group of UK researchers is at the forefront of developing new ways to
diagnose diseases rapidly and cheaply using a technique for measuring
the metabolic response of an organism to a stimulus, writes Simon
Hadlington.

The scientists, from Imperial College London, have already demonstrated
that the technique, known as metabonomics, can reveal the presence and
severity of diseased arteries and certain bone diseases. Metabonomics
can measure the metabolic response to a drug or an agent of disease.

When we take an aspirin, for example, many subtle changes occur in the
cells of our bodies. The levels of various molecules - metabolites -
will rise or fall. Traces of these metabolites will be present in blood
plasma and urine. Advanced analytical techniques, such as nuclear
magnetic resonance, make it possible to build a profile of metabolites
in these samples and to monitor how the profile changes in response to
different stimuli. Similarly, someone's metabolic profile will change if
they are suffering from a disease as it alters their body's
biochemistry.

The researchers say the technology could have important applications in
drug discovery, including reducing the need for live animals in tests.
More ambitiously, they suggest that the techniques could eventually be
developed for "personalised healthcare", where a test could indicate
which medicines would or would not be effective for an individual
patient. "We have used metabonomics successfully to diagnose coronary
artery disease based on its unique metabolic signature," says Professor
Jeremy Nicholson, at Imperial College.

"We modelled metabolic profiles of patients with varying severity of
disease and used these models to produce a diagnostic computer program."
The program detected the presence and severity of the condition in more
than 90 per cent of cases, suggesting the potential for a faster, safer
and cheaper alternative to conventional angiographic screening, which
uses radio-opaque substances. The team has had similar success with
diagnosing bone diseases such as osteoarthritis and osteoporosis and
certain types of cancer.

The tests are now being developed by a spin-off company, Metabometrix,
which already undertakes projects for industry. The researchers are also
using the technology to improve the efficiency of drug discovery. Each
year tens of thousands of chemical compounds are assessed for potential
pharmacological activity. The vast majority are discarded because they
are found to be toxic or ineffective. The sooner these are weeded out,
the better. "We have a huge database of metabolic profiles caused by
toxic compounds," says Prof Nicholson. "We can test a promising compound
in the very early stages using non-invasive methods and if it produces a
profile that indicates toxicity, it can be discarded." Fewer animals
would be required by drug companies. Further ahead, Prof Nicholson
predicts, metabolic profiles of individual patients could predict how
their bodies' unique biochemistry would interact with different drugs.
In this way treatment could be tailored specifically to each patient.

See also: FT.com ; This article at FT.com