Pharmacogenetics – Door Opener for Precise Drug Therapy and Prevention

State-of-the-art data technology networks have established therapy concepts with biochemistry and genetics. The results are new, personalized treatment principles. Even hereditary diseases become less threatening.

Our article describes the complex relationships between pharmacogenetics and drug therapy as well as the consequences for the medical care of people. For easier understanding, we have largely dispensed with technical details and have chosen clear formulations.

Basic information on pharmacogenetics

Every patient wants the best possible treatment for his or her illness. The prescribed drugs should be well-tolerated, and the complaints should be quickly remedied. In the vast majority of patients treated, the drugs used are also reliably effective and rarely show serious side effects.

In addition, however, there are people who do not fit into this pattern and develop severe drug intolerances or do not respond to treatment. There are usually two main reasons for this. One of these is over- or under-dosage of the drug; the other is a genetic disposition. These are by no means major changes in the gene structure of an individual, but rather small and minute deviations of certain gene sequences of individual biomolecules in the human metabolism.

A typical example of this is enzymes that the body uses for drug administration. If the genetic enzyme pattern of a diseased person deviates from the norm, all conceivable disorders are possible when administering drugs. These range from ineffectiveness to severe symptoms.

However, thanks to the latest data analysis methods, it is often possible today to identify these “disruptive enzymes” in order to subsequently provide such persons with a precise medication therapy. These minimal, individual genetic differences are being investigated in the medical branch of research in pharmacogenetics.

Definition and tasks of pharmacogenetics

The word pharmacogenetics sounds mysterious but is easy to decipher: “Pharmako” is of Greek origin and means active substance or drug; “genetics” stands for the theory of heredity. In terms of content, it is about how hereditary (genetic) characteristics influence the effect of drugs. This also makes it clear that such questions always concern an individual who, because of his or her typical genetic characteristics, needs individualized or personalized medicine.

At the same time, these issues define the medical objectives of pharmacogenetics, which include the following points:

Predicting how medicines work in an individual

• Based on this, adapted drug dosage and effect optimization
• Avoidance of ineffectiveness or dangerous side effects of the active substance
• Preventive risk protection of the patient by a different choice of medication

Why gene sequences change

The answer is provided by a look at the history of human development. From the very beginning, nature has arranged the genes in such a way that mutations of different characteristics are permissible. Thus, in addition to very small differences in characteristics between people, such as hair or eye colour, the various populations of our earth also developed.

On the one hand, the human genome determines the outward appearance of a person; on the other hand it determines the internal processes in the body. Examples are the digestion or the utilization of drugs with the associated metabolism. However, the smooth interaction of the individual components only succeeds because the smallest biomolecules such as enzymes perfectly control all processes in the organism.

If, on the other hand, one or more of these enzyme structures are genetically modified, their mode of operation may change and thus impair drug therapy. The body then only absorbs an active substance in ineffective quantities or no longer excretes it properly. As already mentioned, both of these have sometimes considerable consequences for those affected.

The applications of pharmacogenetics in patients

From a purely theoretical point of view and in connection with the digitalization of medicine, it would be possible today to select the perfect drug for each patient before therapy begins. The enthusiasm in the professional world and many health-oriented media initially went in this direction. The fact that human genes were fully decoded for the first time in 2003 contributed to this.

However, this approach is not conducive to achieving the desired results in everyday medical practice. In view of the choice of drugs that are both effective and have few side effects, there is generally no reason to do so. Added to this are the cost aspects of many genetic blood analyses and the increased workload.

Instead, the pragmatic approach has become established, i.e., pharmacogenetics should only be used when problems such as intolerance or ineffectiveness become apparent during routine therapy with drugs. However, in the case of very serious diseases and the use of drugs with known serious application risks, pharmacogenetic diagnostics can be applied even before treatment begins.

Product and treatment examples

The high therapeutic benefit of pharmacogenetics becomes clear in the following examples:

For the treatment of elevated cholesterol levels, substances from the group of blood lipid-lowering agents such as statins are used in many cases today. They are effective and well-tolerated, but in individual cases they can lead to very serious muscle diseases. The Swiss TV health magazine CheckUp provides a meaningful contribution to this in a video, which was produced together with the Hirslanden private hospital group.

Other tried and tested drugs such as psychotropic drugs, blood-thinning preparations, or painkillers can also lead to severe intolerances if the patient has a corresponding hereditary predisposition. Here too, pharmacogenetic testing makes a significant contribution to solving the problem.

In the meantime, pharmacogenetics has also become established in the treatment of many types of cancer. For example, in the case of breast cancer that can be treated with hormones, antiestrogenic agents such as tamoxifen are used. In order for this substance to attack the cancer cells, a specific liver enzyme (known as cytochrome P450) must first activate tamoxifen.

However, there are different individual genetic variants of this enzyme, and not all of them can convert the drug “ready to attack”. Affected women are known as “bad metabolisers”. However, with a molecular genetic analysis, ineffective cancer treatment can be avoided in advance and an effective alternative can be selected.

Status of research and development in pharmacogenetics

Pharmacogenetics enjoys a high reputation in all medical circles, from doctors’ practices to research in hospitals. A major contribution to this has been made by the great amount of knowledge that has been gained since the decoding of the human genome in 2003.

However, this does not mean that medical textbooks have to be completely rewritten because of this innovative branch of research. It has become clear that pharmacogenetics ideally complements and expands existing knowledge but does not replace it. It is also clear that further extensive research and development work will be necessary for years to come for the known active substances and every new therapy and prevention concept.

For this reason, cooperation between pure research institutions, hospitals, private medical institutions, and the pharmaceutical industry is more important than ever. All in all, this will accelerate a development that will gradually advance preventive measures and more personalized medicine in the interest of the sick and insured.

Cost aspects of pharmacogenetics

The knowledge gained with the help of pharmacogenetics is primarily of benefit to the sick individual. This individual receives a drug therapy optimally adapted to his or her situation. At the same time, much more concrete and reliable indications for a targeted prevention of each treated person are created. Today, the abbreviation for this modern, precise form of drug treatment is usually “personalised medicine” or “individualised medicine”.

As a rule, a better and above all novel health care service is also associated with costs that are not covered in each individual case by the compulsory health care insurance of a country. Significantly more leeway is offered here by private health insurance that takes into account personal ideas or business necessities.

The view of the Swiss Federal Office of Public Health FOPH on pharmacogenetics

The FOPH has been closely following the development of pharmacogenetics and the resulting aspects of personalised medicine and prevention for years. This includes lively exchanges with medical research as well as with the health authorities of other countries.

Overall, the FOPH takes a consistently positive view of the development of personalised medicine, and also provides indications for its further development. The future effects of personalised medicine in the Swiss health system are also part of the FOPH’s considerations. In a fact sheet, the Office also describes in a very concrete and compact way how it will deal with this in the interests of Swiss citizens.