Who will benefit from pharmacogenetics research?

Pharmacogenetics is the study of inherited differences in response to pharmaceutical drugs. One of the interesting issues lately has been the "discovery" that people of African-American heritage seem to react differently to drugs intended to reduce high blood pressure. Since the problem is more common among these people than those of other ethnic heritages, there seems to be some benefit to designing "ethnic" blood pressure medication.

What's funny to me is that, since the discovery of this effect, I haven't seen any drugs approved and advertised specifically for African-Americans. Perhaps this is the kind of result James Randerson was thinking of in the article I discussed yesterday, Risks of Online Genetic Testing.

Pharmacogenetics looks like a good thing. With it, doctors could match treatments to patients to speed up cures and minimise negative reactions to medication. Old drugs abandoned because of adverse effects in some test patients could be revived, if the effects' genetic basis can be understood. Ultimately, say evangelists for personalised medicine, your treatment will be tailored to your own genetic makeup. We would see a plethora of individualised panaceas.

As with genetic testing--which I discussed yesterday--Randerson feels the hype doesn't match reality. First, there's no incentive for pharma companies to develop genetic tests for response to an existing drug--unless the test could result in greater use of the drug.

For example, the experimental Alzheimer's drug rosiglitazone, currently in the final stages of clinical development does not appear to help patients in general; but when targeted at specific genetic subgroups it does seem to be effective. The result, to me, sounds like an attempt to save a drug that might otherwise be scrapped after costly clinical trials. I found a similar situation with a drug used against brain tumors: a genetic test--not available to the general public--may determine which patients are more likely to have successful results with the drug. If the test were more widely available, it might give more hope to those expected to be more susceptible to the drug.

For the second reason Randerson feels the hype doesn't match reality, there's the process of drug development. Now, think carefully--if you were a pharma company executive or board member, would you be likely to push further development of a drug that only affects a portion of the potential population of patients? Not likely. This situation is the case sometimes followed by a company who learns that their prospective new drug is metabolised by a family of enzymes in the liver called the cyp450 genes, which break down drugs and toxins. Because the cyp450 genes exist in different forms in different people, the new drug is not likely to be developed further if it is destroyed very quickly by the most common forms of the enzyme.

Yes, there are a fewdrugs on the market that are tailored to the patient's phenotype: the anti-cancer treatment herceptin, which works differently depending on which genes are expressed in the tumour, is in the vanguard; and drugs for psychiatric conditions are also likely to receive the pharmacogenetic treatment. I haven't checked into whether the geneticly determined susceptibility to these drugs was identified pre- or post-development.

So, according to Randerson, neither genetic testing nor pharmacogenetics is apt to dramatically change the medical landscape in the near future. Do you have a comment or opinion to add?

Marie Godfrey, PhD