Germany competing with UK biobank
Blood is to be the new currency of biotechnologists. By comparing of blood DNA, proteins or metabolites, researchers and companies hope to find biomarkers that can accurately predict the onset and the outcome of complex diseases. Assays based on validated biomarkers could allow for earlier treatments of diseases such as cancer, heart disease, diabetes or stroke. This summer, two unique resources for biomarker research took off. Both aim to become the largest biobanks for biomarker research in Europe.
In August, the UK Biobank began recruiting blood donors to participate in building up the world’s largest repository of DNA samples. By 2011, and after an investment of a89.6 million the British will have established a biobank that covers blood samples of 500,000 citizens aged from 40 to 69. To date, about 3,800 volunters have donated 40 milliliters of blood. If the volunteers of the prospective study develop a disease or have died, their blood samples will be analysed. The UK ‘biobankers’ will look for mutations or changes in gene expression the diseased samples compared with those from helathy individuals. They will link the genetic markers with the medical records of the patients and with life style factors, such as nutrition, smoking or Body Mass Index. By comparing the data with those of healthy volunteers, the scientists hope to find biomarker patterns, which correlate with hard clinical endpoints or which can be used to predict the contribution of genes and the environment in the development and prognosis for common diseases, as well as in the metabolization of drugs. The resulting biobank will be offered to industrial contract partners, which develop molecular diagnostics. Currently, the small but hyped market segment (world market: a2 billion, EU Market: a700 million) is expanding at 15% per year, according to estimates from Cambridge Healthcare Advisors.
Tracing disease development
“The concentration on DNA analysis might be well to diagnose patients with genetic diseases. But DNA doesn’t tell us too much about disease progression”, believes Dr. Stephan Rapp, who just recently announced a new biobank project, which could challenge and complement approaches such as the UK Biobank.
In 2002, Rapp changed from Wyeth Corp. to the Bavarian blood donor service of the German Red Cross to build up the ‘Biobank of blood donors’. After a top-secret 3-year pilot phase with Wyeth and Roche Diagnostics as partners, the biobank was made public at the end of June (www.blutspendedienst.com).
“There are two important differences between our’s and the UK Biobank’s approach”, explains Rapp. “In contrast to most biobanks, which focus on DNA analysis, our resource provides serial blood plasma samples from the same blood donor, so-called retain samples of the last 5 years. Consequently, our partners can analyze changes in the protein or metabolite patterns of the same patient before and after disease outbreak. The possibility to conduct ‘kinetic studies’ is unique throughout the world, to my knowledge.” The second reason could bring down the costs of biomarker validation, an important factor in the development of commercial blood assays: About a10-40 million are currently needed to generate a positive return-on-investment for an FDA-approved diagnostic kit such as Roche’s AmplichipP450, quotes the US-consultancy Genomic Healthcare Strategies (Charlestown). “Our biobank already contains more than 3 million blood samples. Infrastructure such as laboratories, logistics or a cryobank are already in place, so that we can work cost-effectively”, Rapp explains. “In contrast, the UK biobank will be dealing with the recruitment of donors, with data collection, and the establishment of infrastructures for years to come. Instead, we only need the consent of our blood donors to use their encrypted samples, and the medical records for biomarker validation.” About 70% of the blood donors gave their consent in the pilot phase.
“By next summer we want to have the consent of 10,000 healthy and diseased blood donors, representing 100,000 blood samples” Rapp told EuroBiotechNews, “When we have worked some 12 months on this basis we will decide whether to expand the biobank to 100,000 volunteers for prospective biomarker analysis.” The interest from researchers and the biopharmaceutical industry is overwhelming. “Every day since the official launch, we have received several expression of interests, mostly from the US.” Rapp knows why: “When I was working at Wyeth we looked for such a biomarker resource, but there was none.”
Market barriers and opportunities
Scientific partners, such as Dr. Friedrich Lottspeich, current President of the European Proteomics Association (EuPA, see p.35), are confident that the plasma bank will provide useful data. There is less variation in the protein patterns of one person than in probes from different volunteers, according to Lottspeich, who is looking for prognostic colon cancer biomarkers in an ongoing project using a new mass spectrometry (MS) method (ICPLTM) to quantify protein biomarkers (LABORWELT 6(4),(2005) 7-10).
However,the complexity and high dynamic range of proteins within blood plasma challenge the development of refined subfractionation and MS methods, which can help to minimize false-positive and false-negative results. Human variation and disease variability together with high costs for the validation of biomarkers may explain, why there are currently more than 150,000 publications on biomarkers with clinical potential but only a handful of validated and marketed markers. Nonetheless, the development of biomarker assays, which measure the response rate for therapies (such as the analysis of the alpha fetoprotein in liver cancer), disease progression (urine proteins in chronic kidney disease) or metabolism and adverse effects of the blood thinner Warfarin (Amplichip P450) point to an era of more effective, efficient drugs which could justify a higher market price. Additionally, biomarkers promise to reduce costs of clinical development by prognosis of drug action, adverse effects and toxicity.
Currently, 12 commercial pharmacogenetic assays are in use for the analysis of drug metabolism/toxicity, 5 for cancer stratification, and 4 elucidate viral drug resistance, according to a JRC study of 2006.