PERSONALIZED MEDICINES: TAILORED TO FIT ‘U’

Imagine, next time when you visit your doctor for treatment, he asks questions like –where do you live and what do you do, in addition to symptoms; before prescribing you a medicine. And ‘YES’ everything is official about it! Maybe because he wants to find the medicine that ‘FITS’ you the best. Here we are talking about the concept of Personalized Medicines wherein “one drug fits all” approach in combination with Pharmacogenomic research can evolve into an individualized approach to therapy where optimally effective drugs are matched to a patient’s unique genetic profile.

Tracing the background of this concept takes us to the term Pharmacogenetics- the term first used in 1959 to describe the discovery that variation in function of a single gene can modify the effect of a medicine or simply it can be explained as “how people’s genetic makeup affects their response to medicines”.

Personalized Medicine can now be defined as a drug tailored specifically to a patient’s genes that is designed to work far more efficiently and with reduced side effects. It is actually the redefinition of diseases on a molecular level so that diagnostics and therapeutics can be targeted to a specific patient population thereby offering right treatment to the right patient. The concept of Personalized Medicines is based on the assumption that drug therapy in genetically defined subpopulations can be more efficacious and less toxic than in the large population.

Before describing how this concept can come into real action, it is essential to visit the basics that started with the huge amount of information stemmed with the Human Genome Project which is well understood now and helped the scientists globally to infer that humans have more proteins than genes and through complex alternative splicing mechanisms, one gene can regulate the synthesis of several proteins. Although human DNA sequences are 99.9% identical to each other, the remaining 0.1% of variation is of great interest. The variations in the structure and function of these genes between individuals are related to differences in the therapeutic response of patients. Other post-genomic techniques played an important role in the foundation of Personalized Medicines which involves the analysis of Transcriptome, Proteome and Transgenics Working of Personalized Medicines starts from Biomarker analysis that indicate a particular disease state can help in classifying subgroups of patients having same molecular variations of the disease, enabling doctor to select an appropriate treatment for the patient. This can be further elaborated via the example of Cytochrome P450 (CytP450). CytP450 is the set of enzymes produced in the liver and one of the most significant factors in each person’s unique response to medicines. These drug metabolizing enzymes are involved in degrading the majority of prescribed drugs, so our personal CytP450 complement is crucial in determining what effect drugs have on us, what dosages are appropriate and what could be the side effects. Apparently, 80% of most serious adverse reactions to medicines involve drugs that are metabolized by the variable CytP450 enzyme system.

Let us take an example of cancer for further clarity of this concept. In cancer chemotherapy of acute lymphocytic leukemia, administration of drugs such as 6-mercaptopurine, 6-thioguanine and azathioprine can cause severe hematologic toxicity or even death in patients possessing a non-functional or null variant of Thiopurine Methyltransferase (TMPT). Functional assays of TMPT in red blood cells or genotyping can identify patients who are homozygous for alleles encoding non-functional enzyme and therefore, unable to metabolize the drugs to their inactive methylated forms. These patients can be safely treated with doses 10-15 times lower than commonly prescribed.

Thus, functional analysis or genotyping provides a more focused or personalized approach in cancer treatment.

The new knowledge of genomics has unleashed the possibility of more effective diagnosis, therapeutics, patient care and consequently, a patient-friendly healthcare system. The idea behind this concept is to develop a focused and personalized approach for treatment wherein variations can be used to understand the general predisposition of certain ethnic groups to particular diseases.

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