Personalized Medicine: Legal Update

Up until now, there has been a big problem in the realm of personalized medicine, with respect to pharmacogenomic analysis, record keeping and access to information. Previously, according to US law, anybody could have access to that information. Meaning: employers and insurance companies could scan your results, or look at your specific genotypes that pre-dispose you to specific illnesses or conditions and discriminate against you for fear of taking on too much risk financially. See my post on ethics of personalized medicine.

As of April 25th, the US House of Representatives voted 420 to 3 in favour of passing the Genetic Information Nondiscrimination Act (GINA), and the senate along with President Bush are expected to approve the act in a few weeks. Undoubtedly, this will be a huge step for the world of personalized medicine. We are already seeing the use of pharmacogenomic markers such as Cytochrome P450 (including the 2C9 and 2D6 variants), warfarin and others that screen for efficacy of drugs such as Herceptin.

It is good timing for this news to come as genotyping is becoming evermore affordable.

Everyone should thank the NHGRI Director Francis Collins for pushing to get this act passed! The act has been shot down twice previously by the senate; hopefully, as the saying goes, the third time will be the charm.

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Prostate Cancer Update: New Gene

A genetic pattern (variation) found on human chromosome 8 has been found to have an association with a 5x risk increase for developing prostate cancer. It is thought to cause 2/3 of African-American cases and 1/3 of Caucasian-American cases of the disease.

Another biomarker might be coming! Pharmacogenomics companies: ready … go!

Full story at

Ethics in Personalized Medicine

Today, I want to highlight a great article I found on the ethical issues in personalized medicine, which is centered around pharmacogenetic information (your specific DNA genotype for a number of specific genes). Firstly, if you want to get up to speed on pharmacogenomics, check out the US government-run Human Genome Project Information site that has some quick Q&A on this topic!

There was an article recently published online by Reagan Kelly, that discusses some ethical issues of personalized medicine, please see some excerpts below:

“Protecting patient privacy is one of the most important things that must be done before ordinary people will be willing to take advantage of individualized medical care, and just about everyone agrees that patient’s have a right to keep details about their health private from most people (even if not from, say, their insurance company or in some cases state or local governments). But how far does that right extend? Does it cover a person’s genetic makeup? That is something that undeniably influences health, and a fair amount of information about what diseases a person has or is at risk for can be extracted from genotype and gene expression information like what would be collected for personalized medicine services. How do you keep that information private and what uses are OK? … Additionally, what about the privacy of other family members? Families share genetic information, and by knowing something about their risk, a person also learns about their relatives’ risks.”

“One of the issues of privacy is also directly related to patient autonomy – the right of a patient to choose what happens to them. The question of what uses of a patient’s data are permissible is not exclusively a question of privacy but also one of autonomy. Is it OK to require a person to allow their data to be used for risk profiling or diagnosis as a condition of performing the service for them?”

“Cost, just like with the policy issues last time, is a significant ethical issue as well. Something like 46 million people are without health insurance today, and many more have insurance plans that cover only the most basic things. How can we provide access to personalized medicine to everyone? Is access for everyone a reasonable goal? Is it an attainable one?”

Please see the full article for more details.

Pharmacogenetics Era: Cancer and Opiate Updates

Pharmacogenetics has “been around since the 1950’s” but, practically speaking, is a new player in clinical diagnosis and treatment, but it is changing the way that healthcare systems, pharmaceutical companies and even small biotechs position themselves in terms of developing new ways to combat disease. With DNA sequencing dropping in price by orders of magnitude, approaches to medicine are in the process of change. Now we are able to start at the genetic level, find out your genotype for a given gene and then recommend certain drugs to you based on your personal genetic profile.

Traditionally, most pharmacogenomic profiling existed with patients needed blood thinners, specifically warfarin, where the Cytochrome P450 gene was tested to determine its presence, mutations and copy number. These features let the physician know your relative rate of metabolism to see how you will respond to the drug and what dosage you should be taking. There are a number of other cytochrome genes that are often included in pharmacogenomic tests now, such as Cytochrome P450 2C9, which is an enzyme that metabolizes coumadin.

I found two examples recently that speak to some advances made in pharmacogenetics:

The first article discusses a new diagnostic called Oncotype DX which looks at DNA of the breast cancer cells to determine if the cells are benign, malignant, or metastatic. The test is commercially available and looks at 16 tumourigenic genes to determine how the cancer is going to behave. This is the tip of the iceberg for the cancer diagnostic market. Look out for more of these test as they are bound to pop up all over the place within the next 2 years. Mark my words.

The second advance is a Nature paper from Clinical Pharmacology & Therapeutics titled Pharmacogenetics of Opioids. They are looking at a number of genes, that, when present or absent, affect a persons dosage requirements. A selection of the article abstract is seen here that speaks to what the paper’s findings indicate:

The polymorphic CYP2D6 regulates the O-demethylation of codeine and other weak opioids to more potent metabolites with poor metabolizers having reduced antinociception in some cases. Some opioids are P-glycoprotein substrates, whereas, ABCB1 genotypes inconsistently influence opioid pharmacodynamics and dosage requirements. Single-nucleotide polymorphisms in the mu opioid receptor gene are associated with increasing morphine, but not methadone dosage requirements and altered efficacy of mu opioid agonists and antagonists. As knowledge regarding the interplay between genes affecting opioid pharmacokinetics including cerebral kinetics and pharmacodynamics increases, our understanding of the role of pharmacogenomics in mediating interpatient variability in efficacy and side effects to this important class of drugs will be better informed.

The pain market is large and vast, with 100-150 million Americans (~57%) having acute and/or chronic pain within the past year. Beyond America, over 500 million cases of pain are diagnosed worldwide each year, and most patients are unsatisfied with current treatment options. The worldwide pain management market symbolizes an escalating trend, having a value of $27 billion in 2004, with an expected increase to $35 billion by 2009. The number of people affected by pain, and have access to pain treatment is likely to escalate with the “baby boomer” generation approaching older age. Also, there is a trend indicating higher incidences of cancer, arthritis, HIV as well as surgeries[1].

There will undoubtedly be the need for advanced pharmacogenetic testing platforms that can determine the drugs that will work best for each individual’s pain need. Be sure to see these diagnostics enter hospitals and genetic labs in a few years!

[1] Frost and Sullivan. (2002) U.S. Pain Management Pharmaceuticals Markets.