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PETBioNewsNewsGenetic tests that improve drug effectiveness are going neglected, warns expert

BioNews

Genetic tests that improve drug effectiveness are going neglected, warns expert

Published 14 February 2013 posted in News and appears in BioNews 673

Author

James Brooks

Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the output from a DNA sequencing machine.
CC BY 4.0
Image by Peter Artymiuk via the Wellcome Collection. Depicts the shadow of a DNA double helix, on a background that shows the fluorescent banding of the sequencing output from an automated DNA sequencing machine.

Genetic tests that could greatly improve the effectiveness of drug therapy for a wide variety of conditions are being underused or ignored, a leading expert says...

Genetic tests that could greatly improve the effectiveness of drug therapy for a wide
variety of conditions are being underused or ignored, a leading expert says.

Advances in
the field of pharmacogenetics -
the study of the genetic differences that influence how we metabolise and
respond to medicines - have led to diagnostic tests that have been slow to gain
widespread use, despite clear advantages.

Dr Ron van Schaik, associate professor and clinical chemist at the Erasmus
Medical Centre in Rotterdam, the Netherlands, founded one of the first
hospital-based pharmacogenetics laboratories in 2005. In the beginning, pharmacogenetic tests were not widely
available. That has changed, and evidence of their clinical usefulness is also
growing.

Nowadays a
simple DNA test can identify patients who, for example, require 10 to 50
percent of the standard dose of a particular drug to avoid severe side effects.
This is true for acute lymphatic
leukaemia patients carrying variants of the TPMT gene receiving 6-mercaptopurine treatment.

Other tests
indicate which patients are unlikely to respond to treatment at all because
their bodies are unable to activate a drug, as is the case with the anti-blood
clotting drug clopidogrel which
needs activation by CYP2C19, or
the cancer drug tamoxifen, which
is activated by CYP2D6. In the
case of HIV (human
immunodeficiency virus) patients, a simple
screen for the HLA (human
leukocyte antigen)-B*5701 gene
variant shows which patients are most likely to suffer severe side effects and
so should be prescribed a different drug.

But
widespread clinical implementation of these tests has been slow. Dr van Schaik says that this is partly
because previously genetic tests have been used mostly to diagnose severe
diseases. 'The general notion that you can do DNA analysis without looking for
a disease is novel, and apparently is an issue', says Dr van Schaik.

'Genetic
tests have mostly been done for rare diseases in clinical genetic centres and
this also induces the belief that the test would be costly', adds Dr van Schaik. 'But a pharmacogenetic
test can be ten times cheaper than a genetic test for a rare congenital
disorder'.

Nonetheless,
health economics can remain a barrier to widespread adoption of the tests. 'In
our hospital', Dr van Schaik explains, 'laboratory tests are paid for by the department whereas the drug
costs go directly from the hospital budget. So the economic benefit of a
pharmacogenetic test is not directly felt by those requesting the test'.

The
implications of pharmacogenetics can be considerable. For example, over 50
percent of all drugs prescribed are affected by common variations in the cytochrome P450 enzymes CYP2D6, CYP2C9
and CYP2C19. The effectiveness of such therapies may well be enhanced by
applying pharmacogenetic information.

Scientific
literature on pharmacogenetic testing has grown greatly in the last
decade. In order to keep up, a group of experts in the Netherlands, including Dr van Schaik, has started an
initiative to perform regular reviews of the literature and publish
evidence-based pharmacogenetic dose recommendations (the KNMP/WinAp group). These recommendations are accessible to all pharmacists
in the country, and are now also available online.

'If you have
one particular gene that affects the metabolism of 50 drugs then practical
information is key', says Dr van Schaik.
'Just knowing what genotype a person has is not enough, you need to know what
you should do with that information. Creating this nationwide system enables
people to interpret the test data and see if the medication they're prescribing
is compliant with the genotype'.

Dr van Schaik discussed his research in a presentation 'Clinical Implementation of Pharmacogenetics: A Seven-Year Experience'
given at the British Society for Human Genetics Annual
Conference on Monday 17 September 2012 at the University of Warwick.

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