Interview: New tools for personalised Dx
Personalised diagnostics open up possibilities for reducing adverse drug effects and choosing the most effective medicine for an individual patient based on a set of biomarkers. While many disease and stratification biomarkers have been identified in research labs using post-genomic techniques, only a few – among them HER2 or KRAS – have been validated by the industry and accepted by regulatory authorities. In November, experts from research, industry and regulatory bodies will come together in Uppsala, Sweden’s hotspot for molecular diagnostics, to discuss novel approaches in the emerging market. EuroBiotechNews spoke with Professor Ulf Landegren, one of the organisers of the 5th Bio Ångström conference (18th November, Uppsala, www.uppsalabio.se), about diagnostics in Uppsala, the opportunities on the horizon, and the bottlenecks in the dynamic field of molecular diagnostics.
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Post-genomic techniques have paved the way for molecular diagnostics. What are the drivers and challenges in this dynamic field?
Landegren:
An important driver is the emergence of biologics – expensive new protein therapies that are directed towards a specific disease target. Targeted therapies provide motivation for a detailed analysis before prescription. A non-responder will not benefit from a targeted therapy. That’s why to identify responders, the FDA and EMA have to approve both an antibody therapy and the appropriate diagnostic biomarker test. We are increasingly able to identify good biomarkers with techniques that emerged from the Human Genome Project. Biomarkers are also important for avoiding failure in late drug development because they identify safety risks or efficacy early in the process. What we will see in the future is diagnostic tests that follow compounds all the way through the drug development process and into the clinic. Compounds will only be prescribed together with a diagnostic test.
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You are a co-organiser of a meeting that will look at these developments in Molecular Dx. How will the Bio Ångström conference address these topics?
Landegren:
The purpose of the Bio Ångström conference is to bring together people from academia and the industry to exchange ideas about needs in the field, the best technologies available, and how they can be applied. Why Uppsala? Well, there is a very long and established tradition of tools development for the analysis of biomolecules here, and several successful entrepreneurs in the field have also come from Uppsala University. We see ourselves as tools developers, and we have many companies in the city: GE Healthcare, Phadia, Gyros and others. So there is a lot of interest in diagnostic technologies here.
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What kinds of technologies are currently at the focus of development?
Landegren:
I can’t describe all of the technologies being pursued by the around 60 diagnostics companies in our region. But I personally believe that measuring different levels of proteins alone won’t be enough to move forward. Instead, I think it will be important to differentiate between very similar proteins – to analyse protein interactions and post-translational modifications. We will get refined answers when we use refined techniques.
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Such as novel probing technologies?
Landegren:
Yes. For example, padlock probes and proximity ligation techniques arose in my lab, and we commercialised them. Padlocks are tools for the analysis of DNA or DNA tags. They are linear probes that turn into circles when they encounter the correct target sequence. They have about the same level of specificity as PCR. But unlike with PCR, you can multiplex these assays so that you can perform up to 50,000 simultaneous analyses. They can be very helpful for gene detection and genome analysis. Recent results used Padlocks to tell transcripts apart in tissues, even when the mRNA molecules differed by only a single nucleotide. That’s very interesting – for instance, to identify the KRAS mutations that are key to screening responders to the cancer drug Erbitux.
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What factors besides technology are key to establishing personalised medicine?
Landegren:
I guess there was a feeling that the market was held back by the reluctance of the drug industry to stratify clients by diagnosing who needs drugs and who doesn’t. Increasingly, I think there is a readiness on the parts of both the regulatory authorities and the large drugmakers to bring out new drugs with diagnostics. And I think the FDA will play a very important role, because most companies view the US as an early market.B