Straight to the heart
Aureus to build database platform for European consortium on drug cardiotoxicity
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PARIS—Aureus Pharma, a privately held knowledge database provider for the life sciences industry, announced in late October that it will participate in a European Commission-funded consortium seeking to develop computer models which predict the effects of drugs on the heart.
The three-year, $4.1 million project, titled "preDiCT: Computational Prediction of Drug Cardiac Toxicity," is being coordinated by the University of Oxford and seeks to create computer models for cardiotoxicity that are intended to help drug developers prioritize lead candidates and avoid drug failure due to adverse cardiotox safety factors. Aureus' contribution to the project will be to use its expertise in Ion Channel/hERG knowledge databases and knowledge management to design, build and populate the platform required for storing the experimental data that will be used to build models, as well as the framework for collecting the knowledge generated in the modeling studies.
"Current best practice in pharmaceutical development relies on the Q-T interval (the spacing of two points on an electrocardiogram) as a proxy for potential danger," says predict project manager Katherine Fletcher of the University of Oxford. "However, it is known that some drugs which fail this test do not lead to arrhythmia, and some drugs which pass this test can still cause arrhythmia. We hope to be able to develop more accurate gauges of potential cardiotoxicity."
To accomplish that, Fletcher says the team will need to push beyond the current state-of-the-art in mathematical models of individual ion channels, which control how and when cells contract; tissue models, which encapsulate chemical processes and physical relationships at millions of separate points in the heart; and the computer code, which must compute these relationships as a series of complex equations, to enable faster-than-real-time simulation of a beating heart.
"Aureus has the skills needed to set up the project's data warehouse, which will integrate information in a variety of formats, run complicated workflows and conduct literature searches to populate the database for our project," Fletcher says.
According to Aureus CEO Jason Theodosiou, the company has been developing knowledge databases for therapeutic drug targets since 2000. Aureus' approach to building knowledge databases includes the analysis of bioassay data and organizing this data in a searchable, relational database. Aureus Pharma has also been involved in a number of other European Commission-funded projects, including the KnowTox Project, which was a Eureka-funded project focused on hepatoxicity.
"Having worked on this project, it was a natural progression to partner with University of Oxford and the other consortium members to work on a cardiotox-related project," Theodosiu says. "High quality data is key to building quality models. The high-quality data that Aureus will provide in the knowledge platform will be the source of data for the model building."
The project as a whole will help accelerate the drug discovery process, he adds.
"Having access to computer models will allow researchers to prioritize, but also ultimately avoid costly laboratory experimentation," Theodosiu says.
Aureus joins a number of industrial and academic research teams that are already participating in the project—F. Hoffmann-La Roche AG, Fujitsu Laboratories of Europe Ltd., GlaxoSmithKline Research and Development, Novartis Pharma AG, the University of Szeged, the Universidad Politécnica de Valencia and the Center for Advanced Studies Research & Development (CRS4) in Sardinia. The consortium is part of the wider European Commission-funded Virtual Physiological Human effort, linked to the umbrella VPH Network of Excellence project. DDN
The three-year, $4.1 million project, titled "preDiCT: Computational Prediction of Drug Cardiac Toxicity," is being coordinated by the University of Oxford and seeks to create computer models for cardiotoxicity that are intended to help drug developers prioritize lead candidates and avoid drug failure due to adverse cardiotox safety factors. Aureus' contribution to the project will be to use its expertise in Ion Channel/hERG knowledge databases and knowledge management to design, build and populate the platform required for storing the experimental data that will be used to build models, as well as the framework for collecting the knowledge generated in the modeling studies.
"Current best practice in pharmaceutical development relies on the Q-T interval (the spacing of two points on an electrocardiogram) as a proxy for potential danger," says predict project manager Katherine Fletcher of the University of Oxford. "However, it is known that some drugs which fail this test do not lead to arrhythmia, and some drugs which pass this test can still cause arrhythmia. We hope to be able to develop more accurate gauges of potential cardiotoxicity."
To accomplish that, Fletcher says the team will need to push beyond the current state-of-the-art in mathematical models of individual ion channels, which control how and when cells contract; tissue models, which encapsulate chemical processes and physical relationships at millions of separate points in the heart; and the computer code, which must compute these relationships as a series of complex equations, to enable faster-than-real-time simulation of a beating heart.
"Aureus has the skills needed to set up the project's data warehouse, which will integrate information in a variety of formats, run complicated workflows and conduct literature searches to populate the database for our project," Fletcher says.
According to Aureus CEO Jason Theodosiou, the company has been developing knowledge databases for therapeutic drug targets since 2000. Aureus' approach to building knowledge databases includes the analysis of bioassay data and organizing this data in a searchable, relational database. Aureus Pharma has also been involved in a number of other European Commission-funded projects, including the KnowTox Project, which was a Eureka-funded project focused on hepatoxicity.
"Having worked on this project, it was a natural progression to partner with University of Oxford and the other consortium members to work on a cardiotox-related project," Theodosiu says. "High quality data is key to building quality models. The high-quality data that Aureus will provide in the knowledge platform will be the source of data for the model building."
The project as a whole will help accelerate the drug discovery process, he adds.
"Having access to computer models will allow researchers to prioritize, but also ultimately avoid costly laboratory experimentation," Theodosiu says.
Aureus joins a number of industrial and academic research teams that are already participating in the project—F. Hoffmann-La Roche AG, Fujitsu Laboratories of Europe Ltd., GlaxoSmithKline Research and Development, Novartis Pharma AG, the University of Szeged, the Universidad Politécnica de Valencia and the Center for Advanced Studies Research & Development (CRS4) in Sardinia. The consortium is part of the wider European Commission-funded Virtual Physiological Human effort, linked to the umbrella VPH Network of Excellence project. DDN
