Diagnostics & Imaging Week Contributing Writer
LONDON The era of personalized drug therapy is inching closer, but the investigations to determine which is the best drug is likely to include a urine test, as well as your genotype.
Researchers in Europe have shown that it is possible to predict an animal's response to a drug from the metabolic "signature" of its urine. The scientists' preliminary investigations on people suggest that human urine, too, holds hitherto untold information about how drugs are metabolized in individuals, based on their intrinsic metabolic profiles.
Jeremy Nicholson, professor of biological chemistry at Imperial College London told Diagnostic & Imaging Week's sister publication BioWorld International: "We have shown a proof of principle that a urinary metabolite profile has the potential to predict whether or not you are likely to have good or bad effects from drugs. If this approach can be fully developed, urine tests of this kind could be used on a huge scale to predict drug metabolism and drug fate, and possibly many other things about a person's health."
The same method could help predict how people will respond to a change in their diet, or even to events such as dealing with a bacterial infection.
"It's potentially applicable to every area of human and even animal medicine," Nicholson added. "It's a completely new way of looking at personalized healthcare for the future a new way of screening people."
Nicholson has been working on metabolic profiling for the past 25 years. He calls the approach "pharmaco-metabonomics" to distinguish it from pharmacogenomics.
The latter is the study of how genomic variations affect the ways in which a drug is metabolized, and whether it is toxic. For example, there are some well-known polymorphisms in genes encoding enzymes that influence how well people can metabolize certain types of drugs. People who cannot metabolize these drugs well may suffer toxic side effects.
But genetic influences on drug metabolism can be very complex, and they are only part of the story. "Pharmacogenomics cannot capture the environmental element," Nicholson said.
The environment includes, for example, the millions of microbes that live on and in humans. Many have enzymes that can metabolize drugs, and they dose the human body with drug-like secondary metabolites, which switch human enzymes on and off. Earlier work by Nicholson's group showed that changing gut microbes caused drug metabolism to change, too.
To address these issues, Nicholson and his team decided to focus on the animal's metabolic profile, as seen in the urine, using nuclear magnetic resonance (NMR) spectroscopy. The strategy involves analyzing the NMR spectra of urine before and after an animal is given a drug, and using the pre-dose metabolic signature to predict the outcome of the drug dose.
Experiments carried out by the group demonstrated that the strategy can work. In one experiment, the researchers conducted NMR spectroscopy on urine samples from 10 rats. They then gave the animals galactosamine. It is a natural metabolite, not a drug, but given in large doses, some rats will suffer liver damage.
Among the 10 rats, six animals developed liver damage and four didn't. Analysis of the pattern of the NMR spectra showed that the animals that fell sick all had a similar type of NMR pattern, while those that remained healthy had a different NMR pattern.
A second experiment involved dosing rats with paracetamol at a level that sometimes causes liver damage. The researchers analyzed the pre-dose NMR patterns of the animals' urine, gave the drug, and then asked a histopathologist to score the level of liver damage.
That approach provided them with numerical values for both the NMR spectra, and the degree of liver damage. "You build a mathematical model that connects all the variables from the NMR spectra the signature to the outcome data on drug metabolism and drug toxicity," Nicholson said. "We found we could take the urine and predict, in a quantitative way, the metabolic fate of the drug and the quantitative level of liver damage."
The experiments are reported in the April 20 issue of Nature in a paper titled "Pharmaco-metabonomic phenotyping and personalized drug treatment."
Nicholson said preliminary tests using human urine, aimed at predicting the quantitative metabolism of paracetamol have had "very interesting" results.
"It looks as if we will be able to apply it to paracetamol," he said. "Future work will aim to find out how many different drug classes can be predicted in this way."
3M Deutschland to acquire SBG
3M Deutschland (Neuss, Germany) reported that it has entered into a definitive agreement to acquire SBG (Berlin), a developer of diagnosis related groups (DRG) software for hospitals, including related trademarks and patents. Terms of the transaction were not disclosed.
3M said this acquisition expands its portfolio in its health information systems division and strengthens its position in the core segments of coding, grouping and quality assurance. The transaction is expected to close in June.
SBG develops software solutions for the healthcare industry in the areas of medical documentation, coding and DRG determination, as well as management. The company's flagship product is KODIP, a coding and grouper software solution for hospitals and funding agencies.
The solution, currently being used in more than 1,000 hospitals in Germany, is compatible with the programs of the hospital IT providers. The successful brand names of the SBG products will be retained under the parent 3M brand name, and the further development of these products will be continued.
SBG will be integrated into 3M Deutschland this year, and the Berlin location retained, the company said.
Elekta receives $11 million order from U.S.
Elekta Synergy (Stockholm, Sweden) said that six of its systems for intensity modulated radiation therapy (IMRT) and image-guided radiation therapy (IGRT) have been purchased by Providence Health System (Seattle). Providence, which operates 18 acute care facilities in four states, signed an exclusive, five-year provider contract with Elekta in September, 2005. Elekta said that the total value of these orders is in excess of $11 million and was booked by Elekta in April.
The six Elekta Synergy systems will be installed at Providence Portland Medical Center (Oregon), Valley Radiation Oncology Center (California) and the new Roy and Patricia Disney Cancer Center (California).
Providence said it chose Elekta Synergy for image guided and stereotactic radiation therapy (IGRT and SRT) based on Elekta's unique technology for integrated 3-D volumetric imaging at the time of treatment.
Providence offers care across a four-state area Alaska, Washington, Oregon, and California. Its services target acute and primary care, outpatient services, transitional care, home and hospice care, substance abuse programs, mental health treatment, comprehensive outreach programs including prevention and wellness, long term care, assisted living, and housing.
Primagen gets expanded CD133 license
Primagen Holding (Amsterdam, the Netherlands), a molecular diagnostics company, reported that the exclusive, worldwide license for the CD133 diagnostic biomarker has been expanded to include the cardiovascular field. Primagen originally licensed the CD133 biomarker from the University of Texas M. D. Anderson Cancer Center (Houston).
CD133 is a genetic expression marker for presence of developing endothelial cells in the peripheral blood circulation and is associated with angiogenesis, the growth of new capillary blood vessels. Clinical research from several academic centers in Europe and the U.S. has shown that CD133 is a promising prognostic indicator of tumor growth.
"New research suggests that the CD133 biomarker can also be used to determine blood vessel growth in cardiovascular disease and to monitor patient progress following surgery" says Bob van Gemen, CEO of Primagen. "In contrast to cancer, where blood vessel growth is associated with disease progression and tumor growth, it is a positive indicator for recovery from cardiovascular surgery. The ability to measure recovery progress can ultimately help physicians better manage patient treatment."
Primagen said it is developing molecular diagnostic products based on the measurement of CD133 expression in peripheral blood cells. By assessing the presence of CD133, these diagnostic tests can help physicians maximize patient treatment.
Primagen has two proprietary molecular product lines on the market: the Mitox products measure mitochondrial DNA and RNA in clinical samples with unmatched accuracy. The Dry Fluid Spot Rainbow product brings HIV-1 viral load measurement to resource-poor environments.