Eighty per cent of pharmaceutical interventions fail in patients even after being successful in animal studies. Musculoskeletal diseases such as osteoporosis, which causes bones to become fragile and more likely to break, dramatically reduce the quality of life of millions of affected patients. We need more efficient and cost-effective treatments for osteoporosis to improve the lives of our ageing population and reduce the strain on the NHS from treating osteoporotic fractures. However, current preclinical assessment is inefficient and expensive.
At the Insigneo Institute, Professor Enrico Dall鈥橝ra is leading a team of researchers developing the first inter-species virtual twin, a new computational framework that includes the observations in mouse experiments and predicts the bone adaptation in human, to identify the best osteoporosis treatments to be tested in clinical trials.
Creating the first inter-species virtual twin
The team will create two parallel virtual mouse and virtual human twins (VMHTs-OP), based on information such as biomedical images, movement analysis and cell data, and use these to predict how bone will change in response to biomechanical and/or biochemical stimulation. Each virtual twin will be based on advanced multi-scale computational models (multi-body dynamics, finite element and cell-population models) to predict how bone changes over time and space due to osteoporosis and in response to new biomechanical and pharmacological treatments. This will help identify new combined treatments that are likely to be effective in patients.
Professor Dall鈥橝ra, Professor of Musculoskeletal Biomechanics in the School of Medicine and Population Health said: 鈥淭he development of new treatments for osteoporosis is crucial for addressing the needs of our ageing population. However, the current preclinical evaluation of combined pharmacological and biomechanical therapies is not only time-consuming and costly but also raises ethical concerns. The creation of interspecies virtual twins in this project offers a ground-breaking approach to preclinical testing. By leveraging fully validated computer models, this project will demonstrate their potential for optimising personalised treatments for osteoporosis and other conditions.鈥
Verifying model credibility for future preclinical applications
The computer models will go through a comprehensive Verification, Validation and Uncertainties Quantification (VVUQ) process to provide the required credibility for future preclinical applications. The model predictions will be validated against longitudinal mouse experiments and available longitudinal clinical data from biomechanical or pharmacological interventions.
A new tool to screen combined treatments using computer simulations
The validated computational framework will be used to test several combinations of treatment regimens (overlap, intermittent, drug holidays) and different interventions (microgravity, high-strain exercises) that would not be ethically or economically testable in animal and clinical trials.
This exciting project will draw on Insigneo鈥檚 advanced expertise in computational modelling and make use of the institute鈥檚 biomechanics and mechanobiology laboratory and preclinical imaging facilities to develop and verify the abilities of multiscale computational models for predicting bone adaptation. The validated models will reduce and partially replace animal experiments in skeletal research which will also lead to a reduction in the cost and time to market for new pharmacological treatments for osteoporosis.
The Virtual Mouse and Human Twins for optimising Treatments for Osteoporosis (VMHTs-OP) project has been selected by ERC-consolidator grant and funded by the EPSRC through the EU Guarantee fund (EP/Z000203/1).
The team:
Open Positions
Please check our vacancies page for current opportunities.
If you are interested in joining the VMHTs-OP project, please contact Professor Enrico Dall鈥橝ra (e.dallara@sheffield.ac.uk)
