Biotechnology Healthcare - June 2008 - (Page 18) PERSONALIZED MEDICINE A personalized drug, on the other hand, relies on molecular diagnostic tests, sometimes called theranostics (therapy + diagnostics), that predetermine a therapeutic target and the likelihood that a drug will achieve the desired response. In Roy’s case, cytogenetic testing confirmed the presence of a biomarker —and indicator of a particular disease — in his case, the Philadelphia chromosome in his bone marrow cells. Ideally, molecular analysis can determine an individual’s disease predisposition and suggest prevention strategies. Here’s how the Personalized Medicine Coalition describes this scenario in its 2006 paper, “The Case for Personalized Medicine”: The molecular methods that make personalized medicine possible include testing for variations in genes, gene expression, proteins, and metabolites, as well as new treatments that target molecular mechanisms. … These tests could offer substantially more information about a patient’s condition, including disease susceptibility and progression, and likely drug response. Due to their predictive nature, the tests may form the basis of more preventive interventions. Personalized medicine includes: • Specialty drugs, including oral products, injectable and infusible agents, and therapeutic vaccines • Diagnostic tests, such as assays that measure the expression of multiple genes, detect genetic variations, and quantify proteins and other molecules in our bodies • Molecular imaging such as positron emission tomography, which produces a three-dimensional image of how the body functions If personalized medicine seems partial to diagnostics, that’s because it is. In fact, all those diagnostics may end up turning the pharma industry on its head. “Let’s say you’re developing an obesity drug and your drug works only in a small subpopulation of obese people,” explains Kenneth I. Kaitin, PhD, director of the Tufts Center for the Study of Drug Development in Boston. “To identify that subpopulation of responders, your diagnostic has to be given to all obese patients. So, you have the potential for a huge market for your diagnostic, but perhaps a small market for your therapeutic.” And as more biomarkers for disease are identified, the reasoning goes, diagnostic tests will come into play not just to verify that an individual will respond to a therapy, but to monitor therapy. “These diagnostics are going to look more and more like chronic-use products,” adds Kaitin. “I wouldn’t be surprised if diagnostics become the new blockbuster products of the future.” 18 BIOTECHNOLOGY HEALTHCARE · MAY/JUNE 2008 PERSONALIZED MEDICINE TODAY People working in personalized medicine rarely say the words “personalized medicine.” They are more likely to think in terms of molecular imaging, or companion diagnostics, the tests that determine if a person will respond to a certain drug. These professionals also may work with gene-expression assays or biomarkers. But “personalized medicine” remains a convenient buzzphrase. Its early definitions tended to focus on the genome, the total genetic information of an individual. Pharmacogenomics, the science of determining the probability of drug response based on an individual’s genome, was considered synonymous with personalized medicine. The MSN Encarta online dictionary still defines personalized medicine as “the prevention, detection, and treatment of disease taking into account a person’s unique genetic profile.” Technically, one could argue that proteins, metabolic enzymes, and RNA are all determined by one’s genome, with due regard given for the influence of environmental factors. But definitions that limit personalized medicine to the genome ignore biomarkers other than genes and genetic variations. Compare the Encarta definition with one from Edwin Clark, PhD, director of oncology biomarkers at Bristol-Myers Squibb, in a 2006 BIOTECHNOLOGY HEALTHCARE article: We want to use whatever tools are available to us. My definition of personalized medicine is “the right drug for the right patient at the right time,” and it doesn’t matter whether it’s genomics or proteomics or a test of how far you can spit that tells you that a given drug is going to be good for you. It doesn’t have to be some fancy genomic test. Personalized medicine now includes proteomics, metabolomics, and transcriptomics, in addition to genomics. These “omics” represent the study of the proteins, the intermediate and end products of metabolism, and the messenger RNA (mRNA) molecules in the human body. Any of these biomarkers can provide valuable information about an individual’s predisposition for disease, enable early diagnosis, predict responsiveness to a drug, and suggest therapeutic targets. INFINITELY MORE COMPLICATED In the excitement following the sequencing of the human genome in 2003, a lot of smart people were convinced that disease cures were just around the corner. Find the gene responsible for a disease, “repair” (gene therapy) or “silence” (microRNA or RNA interference) the gene, and presto! — disease cured. It hasn’t quite worked out that way. Some disorders, such as sickle cell anemia, cystic fibrosis, and Huntington’s disease, correlate with a single defective gene. Most dis-
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