Biomedical research

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Basics

In this section you find out how your genes can influence your response to medicines.

1. What is pharmacogenetics?  
2. What is the goal of pharmacogenetics?
3. How can variations in genes affect the response to medicines?
4. What is the present use of pharmacogenetic tests?
5. What are the limits of pharmacogenetics?


 

1. What is pharmacogenetics?  

Pharmacogenetics studies the genetic variation between people underlying differential response to drugs. Genes determine the make-up of all the body's proteins, and as medicines travel through the body they interact with many of these proteins. 

Pharmacogenetics research explores whether the presence of a particular version of a gene influences the effectiveness or the side effects of a given medication.
 

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2. What is the goal of pharmacogenetics? 

People react to drugs differently. Delivering diagnostics to doctors will allow them to judge how a person will react to a drug before the doctor prescribes it. These diagnostics will help predict how a person is likely to respond to a certain drug, and whether the dose should be changed to get the desired effect.

From pharmacogenetics to advance drug discovery, clinical development, and new diagnostic applications
Pharmacogenetics could also reduce cost and time in the development of new medications, as well as ensure better follow-up once treatments have hit the market.

There is hope that pharmacogenetics will one day allow for the identification of those people for whom a treatment will either be effective or have no side effects. This will allow the possibility of putting medication targeted to specific groups of people on the market. By developing more targeted therapies, more effective and safer medicines will be provided.
 

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3. How can variations in genes affect the response to medicines?

Small, but normal, variations in your genes (scientists call them polymorphisms) can produce proteins that work differently from those of your friends or relatives. This can affect how you respond—or don't respond—to different medicines. How well these proteins do their jobs varies considerably between people.

For example, certain painkillers only work when body proteins convert them from an inactive form to an active one. If these body proteins work too fast, the drug will be eliminated from the body before it has time to work. 

To do their job, painkillers need to bind and modulate a target body protein, the receptor. If the target body protein is slightly altered, the painkiller might not be able to bind. Or if there are too many target body proteins the effect of the painkiller might be too large. 

Fast or slow metabolizer?
Genetic variations in the body proteins that metabolize the particular drug can have severe effects. If the drug is metabolized too fast it will be eliminated from the body before it has time to work. If the drug  is metabolized too slowly it might accumulate to possibly harmful levels.

Whether a person has a slow or a fast metabolizer phenotype has  consequences for the type of drug used:
A prodrug needs metabolization to  become active (eg codeine is metabolized to morphine). In a slow metabolizer phenotype, a prodrug has poor efficacy,  and the prodrug can possibly accumulate. In a fast metabolizer phenotype, the prodrug has a good and rapid effect.

An active drug is inactivated by metabolization.  In a slow metabolizer phenotype, an active drug has a good efficacy, although accumulation of the active drug may produce adverse reaction. The patient may therefore need a lower dose. In a fast metabolizer phenotype, an active drug has a poor efficacy, and the patient may need higher or more frequent dosing.

It takes two to determine the final effect
Both variancy in gene expression of the target body protein (too many receptors, normal, or slightly altered variants affecting binding) and variancy in metabolizer gene type (fast, slow, normal) determine the final effect of a drug: good,  poor, mediate efficacy, and the presence or absence of adverse effects.

 

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4. What is the present use of pharmacogenetic tests?

At this moment, pharmacogenetic research is mainly used for diagnostics, not preventive. When a patient displays an unexpected reaction to a drug, pharmacogenetic tests can reveal why. The tests have not yet or hardly been applied to choose the best medicine for patients in advance. Clinical application, except in rare cases, is not yet underway.


Breast cancer
One such rare case involves the pharmacogenetic drug, Herceptin, which is used to treat some forms of breast cancer. For women who have developed this type of breast cancer, the treatment is very effective, but for others who have developed another form of breast cancer, the treatment has no effect.

AmpliChip
Another example of a diagnostic tool is the AmpliChip™ CYP450 test developed by Roche. This tool will help physicians prescribe some drugs more effectively. The AmpliChip Test can identify variations or common mutations in two metabolizer genes, CYP2D6 and CYP2C19.  Common variations in these genes affect how a person’s body processes many drugs used for some of the most common health problems. This new microarray can be used in the clinic to help decide about treatments. The goal is to prescribe drugs that are most effective and safe for each patient.

 

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 5. What are the limits of pharmacogenetics?  

  • Genetic factors are not the only influence on drug response. Environment and lifestyle are also important factors.
  • The application of pharmacogenetics requires the existence of rapid, reliable, and inexpensive genetic tests.
  • The clinical relevance of genetic variations must be proven.
  • Applications are currently limited to a specific number of treatments for a limited number of illnesses.
  • Health professionals, including doctors, nurses, genetic counselors, and pharmacists, will need to receive training before pharmacogenetics is integrated into medical practice.

 

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With use from HUMGEN and Medicines for you.

Website: Websteen