Applied Biosystems, an Applera Corporation business, has stepped into a collaborative research study with the National Centre for Toxicological Research of the US FDA/NCTR whereby Applied Biosystems will use its Expression Array System and Rat Genome Survey Microarray to investigate the toxicity of a common class of diabetes drugs using samples provided by the FDA/NCTR.

As part of the collaboration, Applied Biosystems will use its Expression Array System to investigate the molecular basis of liver toxicity associated with certain diabetes drugs.

In 2000, troglitazone (Rezulin) was withdrawn from the market due to severe liver toxicity with an unknown mechanism. Troglitazone and other currently marketed drugs, such as rosiglitazone (Avandia) and pioglitazone (Actos), are members of a popular class of insulin-sensitizing agents. The mechanism for troglitazone's hepatotoxicity is currently unknown, and it is also unknown whether or not agents in the same chemical class may cause similar gene expression changes that could lead to similar toxicity.

"Liver toxicity is a leading cause of drug removal from the market," William V. Murray, division president of the Molecular Biology Division for Applied Biosystems said adding, "We look forward to helping the FDA determine the reason for toxicity induced by troglitazone, and to identifying similarities or differences in the gene expression profile triggered by this drug and other marketed or investigational drugs in the same class."

Weida Tong, director of Centre for Toxicoinformatics of the FDA/NCTR said, "The Rat Genome Survey Microarray and other technologies developed by Applied Biosystems will provide us additional means to understand the molecular basis of the potential liver toxicity associated with the glitazone-based Type II diabetes drug family."

In addition to its Expression Array System, Applied Biosystems will use its real-time PCR systems and TaqMan Gene Expression Assays to validate the results and extend the study of identified biomarkers to other samples. The FDA/NCTR plans to analyze the data to identify specific genes and pathways associated with liver toxicity and use identified toxicity signatures from the microarray data to predict the toxicity of future drugs in the same chemical class, the release says.