By Dr. Liam Drew (September 8, 2016)
Personalized Prescription is gaining momentum, but is there enough evidence for it to become standard clinical practice?
For the patient of leukemia ten years Jason Saunders, standard chemotherapy would not work. Given the standard drug treatment, there was a strong likelihood that toxic metabolites accumulate in your body and sick, requiring an interruption in therapy that would allow the return of cancer.
This is because Jason is one of 10% of Caucasians with a genetic variation which reduces their ability to metabolize thiopurine, the most commonly used to treat acute lymphoblastic leukemia drugs. Instead of having two copies of high activity of TPMT gene that produces the enzyme responsible for metabolizing these drugs, Jason has only one.
Fortunately for him, doctors at Children’s Research Hospital St. Jude in Memphis, Tennessee, knew it. When he was diagnosed with cancer, one of the first things that their doctors did was take a sample of his blood to assess how it might respond to drugs. As a result, Jason received a lower dose of thiopurine than normal, and tolerated the therapy without a break. He is now in the process of being declared free of the disease.
TPMT test for leukemia patients is one of the most common examples of treatment to suit the patient genetics, so robustly that predicts the likelihood of adverse effects of thiopurine. The test is now mandatory when this type of chemotherapy begins in many places, and is also recommended before using thiopurine to teat other conditions, such as inflammatory bowel disease and rheumatoid arthritis.
The tests are typically performed only when needed prescribe a drug, but Jason’s experience was different. Instead of proving their status only TPMT, we examined the variability across a number of genes involved in various drug responses as part of the scheme PGEN4Kids Hospital. The results were incorporated into their health records. If ever there is prescribed another drug to which these genes can predict an adverse response, the information will be presented to your doctor immediately. The choice of which drug to use, and in what doses, it can be done immediately without further testing or waiting necessary.
To reach this point, St. Jude and some other research hospitals are doing pilot tests or similar schemes have had to develop a lot of infrastructure, train your clinical staff in how to respond to genetic data, and ensure requiring significant funding these schemes. It was once a distant hope, but now there is optimism among St. Jude doctors, pharmacists and geneticists who have a clinical program that allows genetic information is routinely used to customize the selection of drugs and dosage.
The idea behind pharmacogenetics – that a person’s genes influence their response to drugs – is not new. Its origins are usually traced back to geneticist Arno Motulsky at the University of Washington, Seattle, who in 1957 published an article discussing the implications of the evidence that adverse drug Malaria drug called primaquine reactions, and the muscle relaxant suxamethonium chloride are hereditary and linked to deficits in the activity of specific enzymes.
Throughout the decades, the number of variants of genes that have been found to influence drug responses has increased steadily. Most genes encoding enzymes, as TPMT, metabolizing one or more drugs. It was found that some variants produced toxic drugs; Others made that certain drugs were ineffective. As the list grew, so did expectations. In the 1990s, it was expected that genetic screening could soon establish an era of personalized prescribing that dramatically improve treatment outcomes.
In practice, however, only a handful of specific tests are routinely used in the clinic today. Perhaps the most celebrated envelops the antiretroviral agent Abacavir, which is prescribed to people with HIV. Up to 10% of Caucasians carry a particular version of an immune system gene called HLA-B which gives them a 50% chance of experiencing a life-threatening hypersensitivity reaction to abacavir. As is the case with several genetic variants that affect drug responses, the problem variant of HLA-B occurs at different rates in different ethnic groups.
BIOADVANCE® as Exclusive Representative for Central retrogene Inc., offers pharmacogenetic testing for nearly 100 types of drugs related to treatments for Cardiovascular Disorders, Chronic Pain and Psychiatric Use.