Affymetrix tech to save pharma 'billions'

The project will make use of Affymetrix' whole transcript (WT) gene expression assay to gain a better understanding of the molecular mechanisms that cause DILI - the most frequent reason drugs are withdrawn from the market, or indeed fail to get there.

Testing for potential DILI is part of the FDA's 'Critical Path Initiative' , which guides drug development.

However, there is currently no reliable method to forecast the progression of the various types of DILI.

Affymetrix believes a diagnostic tool to predict liver disease could save pharmaceutical companies around $2bn (€1.27bn) in development expenses in the US each year.

In 2004, Stephen Williams, Pfizer's head of global clinical technology, said the company had wasted $2bn over the last decade on drugs that failed in clinical trials or were withdrawn from the market due to liver toxicity problems.

The Fraunhofer team will initially try to understand the molecular basis of DILI before trying to develop a diagnostic array that can detect the earliest signals of liver toxicity.

"Applying genomic sciences to toxicology can dramatically improve drug safety ," said Professor Juergen Borlack, director of the Fraunhofer Institute of Toxicology and Experimental Medicine (ITEM) and head of the Institute of Pharmaco- and Toxicogenomics at the Hannover Medical School (MHH), who is leading the study.

"The Affymetrix WT technology enables us to see the real biology to better identify susceptible genes and potential gene targets for novel pharmacotherapeutic treatments."

The whole transcript expression profiling approach enables researchers to characterise disease etiology and molecular mechanisms with a high level of accuracy and resolution.

The WT assay is designed to generate unbiased, amplified and biotinylated sense-strand DNA targets from the entire genome present in a sample.

In combination with Affymetrix' GeneChip Exon 1.0 ST and Gene 1.0 ST arrays, the assay enables expression measurement across the entire length of a gene, offering a more complete and accurate picture of gene expression than 3'-based assays.

The protocol employs a combination of random priming, linear amplification and a fragmentation and labelling strategy to generate targets along the entire length of a transcript.

By using the technique to identify gene transcripts involved with DILI the team hope to develop new diagnostic assays and adjunct therapies that will slash drug attrition and drug withdrawls.

"Professor Borlak is recognized around the world for his efforts toward finding new technologies to safeguard drug candidates," said Kevin King, president of Affymetrix.

"We are eager to see the Fraunhofer Institute's results and look forward to the commercialisation of a more effective diagnostic tool for drug-induced liver injury."