A revolution in personalised medicine

The pharmaceutical market is changing fast and industry has been required to move quickly to keep pace with this dynamic situation.

“Small genetic changes can greatly increase an individual's risk of developing disease”

There is, however, a lot of work still to be done, with only 30-60 percent of common drug therapies being successful and up to seven percent of hospital admissions in the US due to adverse drug reactions, many fatal. The trial and error approach applied to drug treatments is no longer a viable option for the industry, for medical practitioners, for healthcare payers or for patients. Biochip array technology (BAT) now offers rapid genetic screening in a multiplex array, to facilitate the drive towards personalised healthcare.

One of the key breakthroughs in the post genomic era is the realisation that small genetic changes can greatly increase an individual’s risk of developing disease, or can influence their response to therapy. This has led to the rapidly expanding field of pharmacogenetics. All the major pharmaceutical companies are now conducting research in this exciting arena and are applying this to all facets of their work, from drug discovery to companion diagnostics.

This is reflected in the increase in the number of submissions to the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) involving pharmacogenetics. There are an increasing number of approved drugs on the market, including tamoxifen, warfarin and 5-fluorouracil, which strongly recommended companion genetic profiling tests before treatment. It is envisaged (and included in FDA guidelines) that pharmacogenetics will become a standard component in drug development in the near future.

Pharmacogenetics testing is currently applied to preclinical investigations of biomarkers for drug response or drug-induced toxicity, including identifying genes with variations that may identify sub-populations. It is being applied to phase I studies to explain outliers or inter-patient variability, to stratify patients into response groups and phase II and III studies to exclude individuals at risk. This allows the development of drugs for specific patient groups with differing clinical genetic profiles. Where new pathways or metabolic influences are discovered, it may lead to the re-investigation of previously failed drugs, if a genetic influence can be established. This will identify niche therapies, adding value to the pharmaceutical back catalogue.

Conversely, poorly metabolised drugs may not benefit the patient in the manner required and accumulate to toxic levels, leading to an adverse patient reaction. Determining the genetic profile of the enzymes known to influence metabolism, such as the CYP450 gene family, can, in combination with traditional indicators, such as age, weight, disease severity etc, facilitate the correct dose of the right drug that most suits the needs of the individual patient. This is the foundation for truly personalised medicine and is where screening for SNP’s in CYP450 genes can make a profound difference to clinical treatment and prognosis.

Genetic testing can follow 3 main pathways; predisposition screening, early detection through population screening and pharmacogenetics, with dual-purpose markers. An example of how Randox BAT can provide a combined approach for clinical solutions is the diagnosis and treatment of colorectal cancer (CRC).

RanplexCRC is a mutation detection assay, utilising Biochip Array Technology (BAT) that can detect CRC at a pre-malignant stage, enabling rapid and effective treatment regimes. This faecal DNA multiplex assay looks for 28 mutations in four genes known to be associated with CRC (APC, KRAS, BRAF and TP53). Detection of any of these mutations will indicate the presence of a pre-malignant or malignant lesion in over 70 percent of CRC’s. KRAS mutations may also determine whether the patient will respond to anti-EGFR therapy, a treatment commonly given to CRC patients. Mutated KRAS genes have been found in 40 percent of metastatic CRC, so this percentage of patients may receive anti-EGFR therapy unnecessarily, unless a primary screen has been conducted.

Utilising Randox’s award-winning biochip array technology, we are working closely with industry experts to develop custom SNP arrays, both for pre-disposition screening and drug metabolism profiling. Randox provide protein, DNA and RNA diagnostic solutions with clinical levels of evidence on platforms that can accommodate basic research (investigator), high throughput clinical screening (evidence) and near-patient diagnosis (multistat). The well-established principles of the assay and test platforms ensure a rapid development time, so assays can quickly be customised to suit the needs of pharmaceutical testing or service laboratories.

For more information, please contact marketing@randox.com or visit www.randox.com.

Dr Martin Crockard is a molecular biologist with a role in both R&D and business development at Randox. Research interests include the development of prognostic expression arrays for breast and ovarian cancer and SNP profiling for predisposition and companion screening for cardiac diseases, cancers etc.