If you are under the impression that the use of individual DNA profiles for making personalized choices for medical treatments lay many years into the science fiction future then it is time to think again. The Roche CYP450 Amplichip will hit the market shortly and will be enhanced over the next 18 months to test for an increasing number of human genetic variations that relate to disease and disease treatment and even to detect viruses.
BASEL, Switzerland, May 7 (Reuters) - Roche Holding AG
intends to roll out six "gene chip" tests over the next 18 months that can help diagnose how patients respond to certain drugs, detect viruses or expose a risk of developing cancer, the company said on Wednesday.
A microarray-based genotyping assay will be described that detects over two dozen allelic variants affecting CYP450 enzyme activity, including those caused by SNPs, frame shifts, multiple base repeats, and even complete gene deletion or duplication.
Individual variations in those enzymes will affect how quickly the liver breaks down drugs. Because of those individual variations there are enormous variation between individuals as to the best dose of a drug to take and even whether a particular drug will work. A person whose body breaks down a particular drug incredibly rapidly may not be able to derive any therapeutic benefit from taking it. Therefore they may benefit more from taking a different drug which they can not break down as easily.
The Roche product will be also be improved by automation so that it can be used in clinics and other point-of-care locations.
The product will include both a set of reagents and a microarray, and will be released in the second quarter of 2003. Initially, the technology will be restricted to use in reference laboratories, to which it will be marketed as an analyte-specific reagent (ASR) set. However, Roche expects that within the next 3–5 years, it will develop the technology into a fully automated system that can be marketed as a certified in vitro diagnostic. The company hopes to eventually bring the test closer to the patient for use in clinical laboratories or even at the point of care.
Jonathan Knowles, head of Roche research, promotes the use of the AmpliChip to reduce the guesswork involved in choosing which anti-depressant will treat an individual case of depression.
"There is a whole series of existing antidepressants," said Knowles. "The probability of anyone responding to any particular medicine is around 50% or even less. The only way to find out is to give someone a particular medicine for a couple of months and see if they feel better. If they don't feel better, then you try another one, and you keep going. There are all sorts of risks and emotional cost to the individual, an emotional cost to their family."
The test checks for genetic variations in genes that code for enzymes in the cytochrome P450 group of enzymes which are involved in breaking down toxic compounds and drugs in the liver and elsewhere in the body.
The new chip from Roche and Affymetrix will test for the most common variations in two genes, CYP2D6 and CYP2C19, which play roles in the way the body handles about 45 percent of the prescription drugs on the market,
This first generation AmpliChip surprisingly does not test the enzyme CYP3A which is the biggest metabolizer of drugs. But looked at from the standpoint of human genetic diversity it makes sense that Roche attached a greater importance to testing CYP2D6 because CYP2D6 is missing in 7% of caucasians and 2% of non-caucasians. CYP2D6 is also hyperactive in 30% of East Africans. Therefore what makes CYP2D6 testing more important than CYP3A testing is that CYP2D6 expression varies more from one person to the next.
This new test kit represents just the tip of the iceberg for the future use of knowledge of personal DNA sequence variations to choose medical treatments.
The testing of DNA sequence variations is not the only way to measure differences between people in gene function. Another way is to test methylation patterns on DNA that the cell uses to control gene expression.
Molecular Diagnostics’ in vitro diagnostics business grew by 14%. However, Molecular Diagnostics’ sales were down 1% overall and thus slightly below expectations as a result of the sharp downturn in sales to the biotech industry (-58%). By signing a licensing agreement at the beginning of the year with Affymetrix on the use of its GeneChip technology, Roche has laid the foundation for future growth in this newly created market. The AmpliChip P450, scheduled for launch in the second quarter of 2003, will be the first DNA chip-based diagnostic test that provides information on patients’ metabolic status. Roche also signed an agreement with the German-based company Epigenomics to codevelop a range of diagnostic tests for the early detection of cancers, their characterisation and prediction of treatment response.
"We are very enthusiastic about this collaboration. Roche is already the world leader in cancer therapies and with this alliance we will complement our position in the diagnostics field. The products that are being developed as part of this collaboration address the urgent need for earlier detection of cancer in bodily fluids by more accurate screening tests, as well as identifying those patients who need chemotherapy and most likely respond to particular cancer therapies," says Heino von Prondzynski, Head of Roche Diagnostics and member of Roche's Corporate Executive Committee. "As the worldwide leader in in vitro Diagnostics we are committed to identify diseases early in order to improve treatment and enhance patients' quality of life. The alliance with Epigenomics will help us to remain at the forefront of the molecular diagnostics market and support our activities to pursue a market that could be greater than 3 billion Swiss francs ten years from now for our divisional cancer care program."
Alexander Olek, CEO of Epigenomics, adds: "This collaboration validates Epigenomics' DNA methylation technology and product development approach. By underlining the synergy between our in-house units, Diagnostics and Pharma Technology businesses, it allows us to pursue our vision of personalizing medicine. With the emerging trend of the pharmaceutical industry moving towards administering therapy only with a specific diagnostic test, we feel that the partnership with Roche Diagnostics solidifies Epigenomics' position as a leader in this field."
DNA testing is no longer just a research tool or a tool to test for rare inherited genetic diseases. It is moving very rapidly into widespread use to allow doctors to make more optimal decisions when choosing treatments for major diseases which have millions of sufferers.
The ability to conduct genetic tests in hospitals and clinics is going to become commonplace in the next few years. Therefore the biggest factor which will determine the rate at which genetic testing increases will be the rate at which the clinical significance is discovered for the hundreds of thousands of genetic variations that exist in the human population.
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