Translational quantitative systems toxicology to improve the understanding of the safety of medicines

A new European research project has been launched which aims to improve the understanding of adverse drug reactions and the approach of systems modelling approaches to drug safety.

Adverse drug reactions (ADRs) are the unwanted side effects of medication. They can contribute significantly to patient morbidity, mortality and hospitalisation costs.

Funded by the Innovative Medicines Initiative 2 Joint Undertaking (IMI 2 Joint Undertaking) the five-year project, called Translational Quantitative Systems Toxicology (TransQST), aims to develop novel computational approaches using the best available data from the public and private domains to address the problems of drug safety.

TransQST is a partnership between ten academic institutions, three Small and Medium-sized enterprises (SMEs) and eight pharmaceutical companies, with a total budget of €16m. The project will be coordinated by the University of Liverpool, and the pharmaceutical company AbbVie is the Project Leader.

One of the main focuses of TransQST are “off-target reactions” which cannot be predicted from the known pharmacological properties of the drug. The main organs of concern for such reactions are the liver, the kidney and the cardiovascular and gastrointestinal systems.

Professor Kevin Park, co-ordinator, said: “The fear of ADRs is a major impediment to the development of new, safe and effective therapies.

“This project will enable us to leverage the best available data and expertise from both public and private domains to generate and validate novel computational models that will help to address the problems of safe drug development.

“Our ultimate aim is to maximise the benefits of medicines and minimise the harm.”

The focus of the TransQST project will be to provide innovative methodologies and software tools for systems toxicology modelling. 

The TransQST project will:

  • Provide fit-for-purpose QST models addressing key toxicity outcomes for liver, kidney, heart and GI-tract.
  • Provide quantitative risk assessment for off-target toxicities in man based on in vitro and in vivo models.
  • Provide a quantitative mechanistic read-across from species (in vitro and in vivo) currently used for the toxicological evaluation of a new drug.
  • Provide definition and applicability of the human physiological and pharmacological relevance of preclinical test systems.
  • Provide a battery of translational biomarkers that can be used for quantitative read-across from in vitro systems to man, and which relate to intracellular pathways (and systems) relevant to drug toxicity.