Marc Bekoff,
Psychology Today / Animal Emotions
March 2018
Colleagues from the University of Oxford and Janssen Pharmaceutica developed original software which predicts the clinical risk of drug-induced side effects for the heart with higher accuracy than animal experiments.
Research published in Frontiers in Physiology (link is external) has won
an international prize for its contribution toward replacing, refining and
reducing the use of animals in research and testing.1
The research, led by Dr Elisa Passini (link is external) and colleagues from
the University of Oxford and Janssen Pharmaceutica, developed original
software which predicts the clinical risk of drug-induced side effects (link
is external) for the heart with higher accuracy than animal experiments.
Early prediction of cardiotoxicity is critical for drug development. Around
40% of drugs that were withdrawn from the market in 2001-2010 had
cardiovascular safety issues in humans. The risk to cardiac safety is
assessed in in-vitro assays and animal models, with a range of species
including rodents, rabbits, dogs and non-human primates being used.
Estimates suggest that more than 60,000 animals are used globally for this
purpose each year.
The ‘Virtual Assay’ software developed by the Oxford team will reduce this
number by improving the identification and elimination of cardiotoxic drugs
prior to extensive animal testing. By using human data, rather than animal
data, the in silico model (link is external) improves how test results
translate to humans and reduces the need for animal experimentation. Rather
than a one-model-fits-all, this software uses a population-based approach,
which is an important step towards personalized medicine (link is external).
Several pharmaceutical companies are already using the Virtual Assay with
promising results, and collaboration with industry is ongoing.
The International 3Rs Prize was awarded on March 12 by the National Centre
for the 3Rs (link is external) (NC3Rs) and sponsored by GSK. The prize
consists of an £28,000 grant and a £2,000 personal award. The same article
also won the Safety Pharmacology Society Technological Innovation Award
2017.
The research was conducted in Professor Blanca Rodriguez (link is external)
and Dr Alfonso Bueno-Orovio’s (link is external) group at the University of
Oxford’s Department of Computer Science, and funded by the Wellcome Trust,
Engineering and Physical Sciences Research Council, CompBioMed project (EU),
TransQST Project (IMI) and the NC3Rs. Professor Rodriguez and Dr.
Bueno-Orovio are recipients of an NC3Rs Infrastructure for Impact grant to
promote the profile of in silico human models for the 3Rs.
The winning research builds on work by the same team, awarded the 3Rs Prize
in 2014. Dr Oliver Britton (link is external) and colleagues then
established a computer model that incorporated variations in ‘normal’ heart
electrophysiological properties based on existing data from rabbit Purkinje
fibres (cardiac cells). Oliver has subsequently been awarded an NC3Rs
project grant to extend the same principles to pain research.
Open to researchers in academia and industry worldwide, the 3Rs competition
recognizes an article published in the last three years that has significant
impacts on the replacement, reduction or refinement of animals in research.
It has been awarded by the NC3Rs since 2005 with sponsorship from GSK.
Reference:
Elisa Passini et al. Human In Silico Drug Trials Demonstrate Higher Accuracy than Animal Models in Predicting Clinical Pro-Arrhythmic Cardiotoxicity. Frontiers in Physiology 12, 2017.
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