Pharmacogenetics and Drug Development

Pharmacogenetics is a fast-evolving field of biomedical research that seeks to identify genetic variations between individuals that alter their response to medications or drugs. As such, it is one facet of the drive towards personalized medicine, where doctors determine the best treatment for patients based on their individual genetic composition as opposed to a "one-size-fits-all" treatment for disease. It is hoped that pharmacogenetics can reduce the number of cases of severe adverse reactions that occur each year and improve medical treatment.

The Basics

• The DNA sequences from any two unrelated individuals are typically more than 99 percent identical; the differences, however, are important in making us unique. Together with our environment, these genetic variations shape our appearance, our personality and our overall health. Differences in our genome can also determine how we respond to drugs or medications. Many drugs are small molecules that work by binding to proteins, the large macromolecules that do much of the work in cells. Small differences in the proteins produced by different versions of a gene that varies from one person to the next can have a major impact in terms of the effectiveness and safety of a drug.

Adverse Effects

• A paper published in 2000 in the British Medical Journal cited an estimate that more than 100,000 patients in the United States die each year as a result of adverse reactions to prescription drugs. Many of these adverse reactions are a result of drug-drug interactions, i.e. taking two drugs that react together to cause side effects; some of these cases, however, are caused by individual variations in the response to a given drug or medication. Determining which genes are responsible for these adverse reactions then testing patients before issuing a prescription might help avoid these problems.

Effectiveness

• Not all drugs are effective in all individuals. The painkiller codeine, for instance, is ineffective in nearly 10 percent of the population, according to the National Institute of General Medical Sciences. The level of response to some drugs can vary widely from one individual to another; much of this variability may be determined by the patient's genetic composition. Determining which genes cause this variability and then testing for common variations would help doctors to prescribe the best medicine for each case, rather than a "one-size-fits-all" approach.

Progress in Pharmacogenetics

• Scientists have already identified genes that affect patient responses to various drugs. The most notable example is probably the cytochrome P450 family of proteins in the liver, which assist in breaking down certain drugs. Genetic variations in the genes coding for these proteins have been linked to variations in how patients respond to drugs like warfarin, an anticoagulant or anti-blood clotting drug. Unfortunately, due to the complexity of human biology and the sheer number of genes that can affect the response to a given drug, much more research will probably be required to make the promise of pharmacogenetics a reality.

Pharmacogenetics Vs. Pharmacogenomics

• Pharmacogenetics and pharmacogenomics at one point referred to separate subfields of research; the two terms are now used interchangeably, however, and both mean essentially the same thing.