Medical Articles

Title: Pharmacogenomics
Date: 07-Oct-2012

By Dr Christopher Ting Chief General Manager, Malaysia/Singapore

Where One Size does not fit All

When I was in medical school, the human genome was still to be mapped. Today, it is difficult to pick up a medical journal without some article discussing the development on predictive genetic testing, pharmacogenomics or personalised medicine. Here, at Gribbles, the still to be exploited potential of personalised medicine has not been lost on us. Headed by Dr Keith Byron and Prof Ian Findlay, scientists at Gribbles Molecular Science (GMS) are developing and commercialising new diagnostic tools in this arena. This article will provide an overview of one area of their research: pharmacogenomics. In a future article, I will provide an overview of another area of GMS's research area: predictive genetic testing.


What is Pharmacogenomics?
Pharmacogenomics is a science that examines the inherited variations in genes that dictate drug response and explores the ways these variations can be used to predict whether a patient will have a good response to a drug, a bad response to a drug, or no response at all.

The way a person responds to a drug (both positive and negative reactions) is a complex trait that is influenced by many different genes. Without knowing all of the genes involved in drug response, scientists have found it difficult to develop genetic tests that predict a person's response to a particular drug. Once scientists discovered that people's genes show small variations in their nucleotide content, all of that changed - genetic testing for predicting drug response is now possible.

The science of connecting drug reaction to genes took a giant leap forward with the discovery and use of SNPs (pronounced snips) in the late 1990s. On their way to sequencing the entire genome of 3 billion base pairs (purine and pyrimidine bases bound together to create the "rungs" across the now-familiar double helix) scientists kept coming upon instances where one member of the base pair differed from the expected. Of the 4 bases that DNA comprises - adenine, cytosine, guanine, and thymine - adenine generally bonds with thymine, and cytosine binds with guanine. About every 1, 000 or so base pairs, scientists observed a mistaken pairing: a guanine paired with a thymine, for example, instead of with a cytosine. These single departures are SNPs, "single nucleotide polymorphisms". What makes SNPs helpful is that certain SNPs are found sprinkled throughout the population, so that by looking at the DNA of individuals who share a certain inherited condition, drug reaction, or susceptibility, researchers can sometimes identify a shared SNP.


The Promise of Pharmacogenomics
Data from the USA alone suggest that 2 million hospitalisations and over 100, 000 deaths occur per year as a result of adverse drug reactions. Right now, in physicians' clinics all over the world, patients are given medications that either don't work or have bad side effects. Often, a patient must return to their doctor over and over again until the doctor can find a drug that is right for them. Pharmacogenomics offers a very appealing alternative. Imagine a day when, after a simple and rapid test of your patient's DNA, you change your mind about a drug considered because the genetic test indicates your patient could suffer a severe adverse reaction to the medication. However, upon further examination of the test results, you discover that your patient would benefit greatly from a new drug on the market, and that there would be little likelihood that your patient would react negatively to it. A day like this will be coming to your office soon, brought to you by pharmacogenomics.


The Gribbles R&D Pipeline
The Gribbles molecular laboratory is developing a range of pharmacogenomic assays to enable clinicians make better, informed decisions about the type and dose of medicines they prescribe.

The first of such tests to be offered is the cytochrome P450 genotyping assay that can identify patients who have a reduced capacity to metabolise Warfarin. About 60 percent of all marketed drugs are broken down in the body by the cytochrome P450 family of enzymes. Individuals vary greatly in the efficiency of their P450 enzymes: Some people are poor metabolisers, while others metabolise very quickly. An individual's CYP450 profile could thus predict if he or she will experience side effects when given a particular drug or not respond at a particular dose.

It is GMS's mission to develop a wide range of low-cost automated pharmacogenomic tests in the coming months and years. In the coming months ahead, GMS will be developing assays for other drugs. While much of the data available currently applies to Western populations, there is considerably less data available on Asian populations. Herein, an opportunity lies for interested healthcare providers and healthcare institutions to participate in clinical trials to evaluate drug dosage responses for some of these newly developed assays.

We will keep you abreast on developments in this exciting area as they arise.

For more information on GMS diagnostic tools please contact your MLO or visit http:/ /www.gribblesmolecular.com/

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