Labs to benefit from Toxicology-On-A-Chip tool
toxicity before they advance to pre-clinical stages, has taken one
step further towards commercialisation as the technology promises
to aid laboratory researchers in weeding out unsuitable candidates
earlier during the drug discovery process.
The tool gains greater urgency considering recent recalls of popular prescription drugs over toxicity issues. Added to the growing costs of drug research and development, the prospect of filtering out candidates with zero potential as early as possible would confer numerous advantages.
The Metachip, (metabolising enzyme toxicology assay chip), developed by Researchers at Rensselaer Polytechnic Institute, University of California-Berkeley, and Solidus Biosciences, is about to begin the second phase of funding for the National Institutes of Health (NIH)-supported project with a view to bringing the product to market within a year.
The researchers believe the technology will be suitable for pharmaceutical and biotechnology companies, who are actively involved in the compound screening process.
"Weeding out toxic compounds earlier would also allow pharmaceutical companies to evaluate more compounds and more efficiently identify those that are most likely to become successful drugs," said Douglas Clark of the Chemical Engineering Department at the University of California-Berkeley.
The Metachip works by mimicking the human metabolic process in the liver, which is where food and pharmaceuticals are broken down, neutralised and excreted by enzymes.
In rare cases some of the metabolites produced are toxic, and this toxicity can be difficult to predict or find at early stages of drug discovery with current testing methods.
The MetaChip uses a culturing method by combining enzyme catalysis with cell-based screening on a single microscale chip.
The drug candidates are added to a chip containing approximately 2,000 combinations of eight enzymes used in human liver metabolism and then sandwiched with a slide of human organ cells in order to detect toxic reactions to the compound.
When toxic reactions are detected, the toxic drug compounds are eliminated as potential candidates for further development as new pharmaceuticals.
"The relatively slow pace of technology development in toxicology and clinical safety evaluation that could be used in early phases of drug development continues to hinder the progression of lead compounds to pharmaceuticals," said Jonathan Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer.
"In addition to safety concerns, drug discovery is an extremely costly process with more than $1 billion (€832 million) invested in each approved drug. For the first time, the MetaChip can enable the initial and high-throughput analysis of metabolism-induced toxicology to be performed before significant resources are invested in the drug's development."
The researchers added that they were also working to develop an automated MetaReader device to quickly analyse the results.
Dordick, Clark, and collaborators published findings on the MetaChip in the Jan. 25, 2005 issue of Proceedings of the National Academy of Sciences in a paper titled "Metabolizing Enzyme Toxicology Assay Chip (MetaChip) for High-Throughput Microscale Toxicity Analyses."
The peer-reviewed publication defines the technology and results of testing in more detail.