Pharmacogenetics
Pharmacogenetics is the study of how genes affect the way people respond to medicines, including antidepressants, chemotherapy treatments, asthma drugs, and many others. The ultimate goal of pharmacogenetics research is to help doctors tailor doses of medicines to a person's unique genetic make-up. This will make medicines safer and more effective for everyone.
Pharmacogenomics is a broader term used to describe the commercial application of genomic technology in drug development and therapy.
Polymorphism is a term given to the naturally occurring variations in the DNA sequences of genes in a population. Investigation of polymorphisms is at the heart of pharmacogenetics. A commonly investigated polymorphism is Cytochrome P450, (abbreviated hereafter as CYP), an enzyme present in liver tissue. CYP is the enzyme responsible for metabolising between 30 - 40 common drugs in use. Differing CYP polymorphisms influence the rates of drug metabolism and therefore plasma levels. Thus it can be seen that a standard dosage of a particular drug can lead to too little, the right amount, or too much drug depending upon the genomic mix of each individual.
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According to a recent study (Journal American Medical Association 2000 Jul 26;284(4):483-5), in the US, 250 000 people die each year from iatrogenic (i.e., physician-induced) causes. 106 000 of these people die as a consequence of non-error, negative effects of drugs. This makes drugs the fourth leading cause of death in the United States each year. |
Uncovering differences in people’s genetic make-up will help doctors prescribe the right medicine in the right amount for each person, making today’s medicines more effective for everyone. The payoff will be preventing unnecessary illness and saving lives lost from the “one-size-fits-all” medicine dosing that is common today. A bonus of this type of research will be an increased understanding of the genes that cause or contribute to diseases such as cancer, heart disease, diabetes, depression, and asthma. This research will also help scientists design new strategies for making the most effective and safe, future medicines.
A diagnostic product that enables a drug to be selectively prescribed possibly would provide cost savings to the health care providers. Other potential benefits would be to increase drug efficacy, reduce follow-up and doctor visits, eliminate costly ineffective drug alternatives, eliminate prescription by trail-and-error and eliminate possible drug toxicity at "normal" doses in non-metabolisers.
What does POCT have to do with pharmacogenetics?
In all probability, the decision-making processes associated with pharmacogenetics will be made at or near the patient's bedside. In other words, a sample of blood or other type of genetic material will be taken from the patient and analysed for their genotype at the bedside, not in the lab. A micro-array or DNA chip technology may be used to probe for the patient's polymorphic characteristics. A search will then be made through hundreds of thousands of stored genetic variations and drug profiles to find the pre-determined drug stategies that best suit the patient.
A computer algorithm will be used to reach a quick conclusion, tailoring the best treatment for the patient, ensuring minimal toxicity and maximal efficacy.
What of quality control or operator competency? These are questions for the future but there is no doubt in anyone's mind that future drug regimes and even patient diagnoses will be made on evidence accumulating from polymorphism and genetic makeup. And this will happen in a POCT environment.
Perhaps by the year 2020 or even sooner, diagnoses of patients illnesses will be made by molecular genomic testing rather than clinical symptoms. Will the cost of this be prohibitive? Will it ever drop to a cost-effective level, comparable to current laboratory test costs? No one really knows. Currently very few laboratories offer any sort of service in this vein. [Please excuse the bad pun ;-)].
This technology is in its infancy. An analogy has been made between pharmacogenetics and personal computers: pharmacogenetics is now at the stage where personal computers were in the early 1980's. And pc's never really took off until sophisticated software capable of doing what most people wanted- word processing, data handling, number crunching- was invented. What we lack today in the field of pharmacogenetics is the "software". A new type of diagnostic technology, not yet discovered, will be necessary for mass screening of thousands of genes on thousands of patients on a low cost/high volume turnover.
Researchers in the field are quite confident that this new technology is on the horizon. When it comes along, diagnostic medicine will change forever.
Click on this link for more information about pharmacogenetics and pharmacogenomics. (This link will take you to the AACC website, on the world wide web).
