Diagnostics

Medical devices and diagnostics are increasingly being relied upon as gating factors on the choice of drugs to treat chronic and acute conditions, signalling a shift in the balance of power between ‘pharma’ and ‘med tech’.

Case study: Getting Personal in Cancer Diagnosis

Technological innovations are underpinning a new cancer profiling service at UCL Advanced Diagnostics. As anti-cancer drugs increasingly target specific mutations, genetic profiling is rapidly becoming the standard way to characterise tumours. Taking advantage of advances in DNA sequencing technology, researchers at UCL Advanced Diagnostics (UCL-AD) – a cancer diagnostics service embedded within the UCL Cancer Institute – have teamed up with the Sarah Cannon Research Institute to offer a rapid and convenient new DNA-based cancer-profiling service. As well as helping doctors choose the most appropriate therapies, the service will also provide a gateway for patients to enter clinical trials of new anticancer treatments.

New cancer drugs are typically both powerful and expensive, so there are good clinical and financial reasons why they should be given only to those likely to respond. Building on UCL-AD’s existing genetic diagnostic service in cancer, the new approach has two key advantages. First, the new method screens for mutations in multiple genes implicated in cancer – 11 initially but with another 20 or so to be added in the near future. Traditionally, genetic tests have been restricted to individual genes, but for the same cost UCL-AD’s new test will screen an array of genes for which genetic information can guide choice of therapy.

The second significant advantage is that the UCL-AD approach uses standard biopsy material gathered in routine clinical practice, ‘formalin-fixed paraffin-embedded’ tissue. UCL-AD researcher Dr Rifat Hamoudi has developed new amplification methods to handle the tiny amounts of degraded material present in such samples. Other tests typically require fresh or frozen samples from patients, but the use of standard materials means that the genetic profiling can be readily integrated into existing pathology work practices and patients will not have to undergo additional invasive biopsies for genetic profiling.

As well as the detection technology – which works with as little as 1 ng of degraded DNA – Dr Hamoudi has developed a supporting bioinformatics and reporting pipeline. Within seven working days, doctors receive a user-friendly report, which they can use to guide their choice of treatment. UCL-AD is able to analyse at least 10,000 samples a year, from UCL-associated hospitals, other UK clinical centres and even internationally.

The new service, to be run by Professor Adrienne Flanagan, has been developed with the Sarah Cannon Research Institute, which manages a range of clinical trial facilities in the UK. A significant advantage of this arrangement is that genetically profiled patients will be able to enter clinical trials of experimental new therapeutics managed through Sarah Cannon. Hence the bank of mutations included in the test will continually be expanded, to include genes associated with approved therapies but also those that could guide entry into clinical trials of new treatments, including those developed at UCL. As additional genetic markers are added, they may also reveal factors associated with success or failure of targeted therapies.

Case study: Prof Francesco Cordeiro – the retina as a diagnostic tool

Visualising cell death in the retina may provide a way to diagnose not just eye disease but also neurodegenerative conditions such as Alzheimer’s and Parkinson’s disease. Combining research with clinical practice as a consultant ophthalmologist at the Western Eye Hospital has given Professor Francesca Cordeiro a clear view of clinical priorities. The need for a simple diagnostic for glaucoma, for example, prompted work on labelling of dying cells in the retina. The resulting technology, however, has turned out to be of wider application.

Glaucoma, raised fluid pressure in the eye, is a common cause of sight loss. However, it is challenging to assess clinically, and its impact is monitored through changes in vision, which are difficult to measure sensitively and a sign that considerable eye damage has already occurred. A tool that could detect early signs of glaucoma would therefore be clinically useful. But it would also greatly aid clinical trials assessing the impact of new interventions.

Glaucoma leads to the death of retinal ganglion cells (RGCs). RGCs undergo a controlled process of programmed cell death, which leads to the appearance of particular lipid molecules on the cell surface. These lipids are bound by a specific protein, annexin 5. Hence Professor Cordeiro realised that fluorescently labelled annexin 5 would provide a way to identify apoptosing cells and hence the onset of glaucoma. During the past five years, Professor Cordeiro has been developing the technology – known as DARC, or detection of apoptosing retinal cells – for use in humans. A key advantage of the technology is that it can be used with minor modification of standard ophthalmological equipment. With safety and toxicity studies completed, phase I studies for glaucoma are scheduled for 2014.

Furthermore, RGC apoptosis is also a feature of neurodegenerative diseases such as Alzheimer’s disease – another area where there is a great need for a reliable and simple diagnostic test. Alongside the work on glaucoma, Professor Cordeiro has also been exploring the potential use of DARC in neurodegeneration, showing in various animal models of disease that the degree of eye damage picked up by DARC corresponds well with damage to the brain.

If the glaucoma phase I trials go according to plan, Professor Cordeiro hopes to extend phase II studies to include Alzheimer’s disease as well as glaucoma patients. The glaucoma studies have provided a further spinoff opportunity. The label is currently delivered to the eye by injection, but Professor Cordeiro has been working on a new non-invasive delivery system, which again she hopes to rollout in phase II studies. Furthermore, the delivery system could itself be a valuable platform technology for delivery of drugs to the eye. UCLB is currently discussing with Professor Cordeiro the possibility of establishing a spinout company to commercialise the drug delivery technology.