Despite advances in biochemistry that have led to medications such as Prozac and Viagra, even blockbuster drugs may fail to treat large segments of the population. More worryingly, in certain individuals normal doses of a particular drug can be dangerous and, in extreme cases, fatal. But with modern analytical tools at their disposal, clinicians can often now explain why a wonder drug for one patient is a useless pill - or even a potential danger - for another.
A new branch of medicine known as pharmacogenomics is emerging to account for genetic differences in the development and prescription of pharmaceuticals. In the past, many of the reasons behind variations in individual reactions to medicines were poorly understood. Some differences between the responses of racial groups to treatments may have been identified, but beyond that scientists were left scratching their heads.
While factors such as age, gender and diet play a part in determining how an individual will react to drugs, genes also play an integral role. Genes that regulate the liver, and in particular the function of enzymes - proteins that speed up chemical reactions - are of particular importance to pharmacogenomics. An enzyme called CYP2D6 influences how well the body breaks down a quarter of all prescription drugs. Scientists have discovered that the gene regulating this enzyme is located on the 22nd chromosome. About seven per cent of Caucasians and one per cent of Asian people are estimated to have a genetic make-up that means they produce a poorly functioning version of CYP2D6.
In other cases, the opposite occurs, and the patient has an errant form of a gene that produces faster-acting enzymes that, in turn, cause them to metabolise the drug too quickly. North Africans and Middle Easterners have a greater risk of being these "ultrarapid" metabolisers. With some medicines, this leads to the build-up of the drug in the patient's system, sometimes causing serious side effects.
Drugs such as the antidepressant Prozac, the blood pressure medication Toprol, and the allergy medication Claritine, are all metabolised by CYP2D6. However, according to Dr Belal al Shammaa, a consultant endocrinologist and diabetologist at the American Hospital Dubai, testing for adverse drug reactions is usually too expensive to be carried out routinely. "We do genetic testing for specific diseases where we know where the gene is," he said, adding that testing for a variation in a single gene could cost as much as Dh1,000 (US$272).
But in some cases, such tests can save lives. Certain forms of breast cancer are linked to an abundance of copies of the HER2 gene. If there are more than two copies, cells may divide more quickly and grow unregulated, resulting in cancer. If patients are tested and found to have high levels of this anomaly, they can be treated with a medicine called Herceptin, effective for that specific type of breast cancer.
Just as patients can be tested to see if a particular treatment will be especially beneficial to them, certain at-risk individuals can be screened genetically to determine if they will react poorly to a drug. Prof Magnus Ingelman-Sundberg, a professor of molecular toxicology in the department of physiology and pharmacology at the Karolinska Institute in Stockholm, said that with Prozac, for example, testing was not worthwhile because the relationship between the person's genotype and the dose they should receive "is not that direct".
One study concluded that more than 100,000 people die each year in the United States as a result of having an adverse reaction to drugs, despite the lengthy trials insisted upon by the Federal Drug Administration before a drug can be made commercially available. Less expensive genetic testing could potentially lower the risk of these reactions. With very good progress being made in developing tests and improving their predictive value, it seems likely that screening could become more common in future. Prof Ingelman-Sundberg said genetic testing was already 100 per cent reliable for some drugs as a predictor of how a person's body will react.
In as few as five years, Prof Ingelman-Sundberg said, genetic testing of patients could be much more prevalent. This view is shared by Dr Shammaa, who believes genetic testing has the potential to transform medicine by its ability to identify adverse drug reactions and, in particular, to indicate diseases that individuals are susceptible to. "At the moment, only a few hundred genetic markers have been developed. In the future, there will maybe 20,000," he predicted.
Dr Shammaa said the information from these thousands of polymorphisms will eventually be used routinely by clinicians. "If you know upfront that such a medicine will have side effects, the GP will say: 'Don't give this medicine.' Or we might know upfront that the medicine will be effective. We can say this patient is suitable for this drug and this patient isn't," he said. "That's what we're hoping for with genetic mapping, but it will take a little bit of time. Right now, it's a lot of money, but these tests will be developed and will become cheaper. This is probably the future of medicine."
@Email:dbardsley@thenational.ae
