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Sun, July 2, 2006 : Last updated 22:07 pm (Thai local time)



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Home > Opinion > DNA chips to find optimal treatment for every patient





WATCHDOG
DNA chips to find optimal treatment for every patient

Thanks to the advent of DNA chips and advances in the field of pharmacogenomics, says Dr Thongchai Thavichachart, president of the Thailand Centre for Excellence in Life Sciences (Tcels), it is now possible to test the effectiveness of a drug on individual patients before doctors prescribe it.

And according to Swiss healthcare giant Roche, one of the world's first such products is the AmpliChip CYP450, jointly developed by Roche and California-based Affymetrix. The basis for the development of this DNA chip was pharmacogenomic data on the influence of the genes for the cytochrome P450 family of enzymes on the efficacy and tolerability of drugs.

This DNA chip is quite tiny - smaller than the size of a business card. At the centre, it has one square centimetre of glass on which a drop of blood is placed to conduct the test.

At the present stage, the CYP450 chip is capable of identifying the most important variants of two key members of this group of genes.

Dr Thongchai says the pharmaceutical industry has long been aware that the effectiveness of drugs can vary greatly among individual patients due to metabolism and other factors. The absorption, conversion and breakdown of drugs are more favourable in some people than others, so the drugs tend to be more effective.

In addition, some drugs may have dangerous side effects on some patients, so it is useful to test a patient's DNA for a drug reaction before it is prescribed. The AmpliChip CYP450 is good for testing the genes for the cytochrome P450 family of enzymes.

According to Roche, most of the differences between people's reactions to drugs are at least partially due to differences in their genes. If the genetic causes of such differences can be ascertained, treatment can be adjusted accordingly. In addition it may even be possible to develop tailor-made drugs for people with certain genetic characteristics. Such drugs can be expected to work more specifically and thus be safer and more effective.

In the case of cytochrome P450, it is important for the efficacy and tolerability of many drugs, as the task of this family of enzymes is to render water-insoluble substances, including many drugs, water-soluble. In addition, molecules are prepared for excretion from the body in this way.

As the function of cytochrome P450 enzymes varies from person to person, drugs are broken down more rapidly in some individuals than in others and their action in the body varies accordingly.

In this respect, at least 50 separate genes and hundreds of gene variants are currently known to "code for" this family of enzymes, and recently it has become possible to detect the most important variants of two key members of this group, resulting in the development of the AmpliChip CYP450.

As in the case of cytochrome P450, DNA chips will in the future have applications in many areas of medical diagnosis - basically wherever genes play a role in the development of a disease. Besides the factor of metabolism, it will be possible to detect the action of different genotypes in cancer, of the group of genes that play a role in reaction of the body to infection and of genes that influence individual susceptibility to pathogens.

In these areas, DNA chips will allow more precise diagnosis on the genetic basis of diseases. With increasing knowledge of genomics and the molecular basis of disease, these chips will contribute to earlier detection, more effective treatment and possible prevention.

However, Roche notes that there remain some obstacles to be overcome. One is that most DNA chip-based tests are still too expensive for routine use. For instance, says Dr Thongchai of Tcels, the AmpliChip CYP450 currently costs more than Bt10,000 per use since it is not reusable.

Even so, it is expected that future versions of DNA chip-based tests will become more affordable and that in the next few years DNA chips will play an important role in medicine.

 Nophakhun Limsamarnphun

 nop1122@yahoo.com








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