Monday, January 30, 2006

Personalized Medicine (PGx)

A major obstacle in the pharmaceutical treatment of depression is the long and bumpy road to finding a drug regime that works for the patient. Bad drug side effects are a major reason for patient noncompliance with drug therapy. Roche Pharmaceuticals, I mean, Roche Diagnostics, has recently announced a new genetic diagnostic instrument that is designed to help doctors treat depression called the “AmpliChip CYP450 Test”. It was approved by the FDA last year and is just available. According to the Roche site, it is the world's first pharmacogenetic microarray-based test approved for clinical use.

Now what is pharmacogenetics? Pharmocogentics emerged in 1950’s when it was noticed drug reactions run in families and researchers started to correlate genetic variation with response to specific meds. It was thought that if a physician would use a genetic test to predict how each patient would respond to the drug before prescribing it, she could tailor make a pharmaceutical regimen that would work best for that particular person; work best would mean that the drug would not harm (reduce side effects) and the drug would help. The goal of pharmacogenetics is personalized drug therapy based on diagnostic tests to predict patient’s response to specific drugs based on genetic profile

Closely related to pharmacogenetics is pharamogenomics. It combines pharmacogenetics with genomic studies. This research started when it was realized that people vary in response to prescribed meds and people vary in response to getting certain diseases. Research studies in pharmacogenomics aim to reveal how different drugs interact with multiple gene populations. Matching drug candidates with patient populations by pharmacogenomic screening will reduce time and cost involved in drug discovery. Lots of money is to be saved by pharmaceutical companies here.

Pharmaceutical industry people say that, “This [pharmacogenetics] is not a fad," (Gualberto Ruano, CEO of Genaissance Pharmaceuticals); "It's a major tidal wave changing the entire pattern of health care."

However, a major report recently offered by The Royal Society (UK), “Personalized Medicine: Hopes and Realities”, says that the impact of personalized medicine is at least 15 years away. The three objectives of PGx combined are to : 1) Reduce drug side effects and improve drug efficacy; 2) Lead to prevention strategies by estimating risk of getting disease; 3) Reduce cost and time of drug development process. The technological, clinical, and ethical obstacles, however, are great.

There is no cheap single molecule DNA test in existence. Recently, however, J. Craig Venter, the genomics entrepreneur who paced the U.S. government to the completion of the Human Genome Project, announced that he hopes to offer $10 million as a prize (he originally pledged $500,000) for automated DNA sequencing technology that can decode a human genome for $1,000. Clinical and ethical challenges include: What level of knowledge is adequate for the patient and the physician to go ahead with the procedure? How will this potential treatment affect other treatment choices? A physician may think that a novel, expensive drug treatment not appropriate, and the health insurance company may not pay for it. But a patient who is dying may think it is worth taking for the slight chance it offers. Who should decide? Who will administer the genetic test, where will the genetic information on the patient be stored, and who will have access to it? As we well know, the nature of data is that it is pervasive and permanent. In order for informed consent to be realized, a patient will have to understand among other things the relationship between DNA and disease, will we have enough genetic counselors trained to do the job? What about the issue of returning benefits to persons or communities whose genotypes made the drug development possible? For more see the World Health Organization (WHO) Human Genetic Programme: Review of Ethical Issues in Medical Genetics.

But even if we had the an adequate knowledge of the genome, a cheap DNA test, a battalion of trained at the graduate level people to explain tests and their meaning to patients, and effective laws in place to secure privacy, what this information means at a diagnostic level is still open. According to Technology Review, while several new genetic diagnostic tests have hit the market in the past two years, doctors will need to learn how to incorporate them into their clinical practices, and scientists will have to figure out what kind of guidelines doctors need to do this properly.

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