The UK’s National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) has awarded grants of up to £100,000 each to 17 R&D consortia in the latest set of challenges under the Centre’s CRACK IT open-innovation scheme.
Launched in September 2011, the competitive funding programme brings together industry, academic institutions and small and medium-sized enterprises in exploring new technologies that can contribute to the replacement, refinement and reduction of animal research in the life sciences.
The competition is being run through the UK’s innovation agency, the Technology Strategy Board, as part of the Small Business Research Initiative, with a total budget of £7 million.
This includes £2 million from the Technology Strategy Board – double its contribution to last year’s challenges, when the NC3RS added a Phase 1 proof-of-concept stage to the CRACK-IT platform.
The introduction of staggered CRACK IT funding approach enables applicants to consider higher-risk, more innovative technologies and improves the chances of viable products emerging from the programme, the Centre noted.
The 17 Phase 1 finalists will have six months to develop the most successful proof-of-concepts for each of the five preclinical challenges. The winning group will get a three-year contract per challenge of up to £1 million for further development and validation.
Identified in collaboration with pharmaceutical companies such as GlaxoSmithKline, Pfizer and Roche, the latest round of preclinical challenges focuses on developing new non-animal assays for drug safety; a virtual infectious-disease research platform; and reducing animal use in the development of chronic inflammatory disease treatments.
One of the challenges (the UnTangle project), sponsored by dementia research charity Alzheimer’s Research UK as well as Eli Lilly and Janssen, seeks to reduce by thousands the number of transgenic mice used each year in Alzheimer’s-disease research focused on the tau protein.
Four UK research groups at the Universities of Aston, Cambridge and Manchester and at University College London will compete on the first phase of development of a physiologically relevant neuronal assay derived from human stem cells.
This assay would be used instead of animal models in early drug development to predict the efficacy and unexpected pharmacological effects of new compounds targeting tau in Alzheimer’s disease.
The other challenges are:
Virtual infectious-disease research: developing a virtual platform to model infection and host response in an individual animal.Typically, a rodent study to test the efficacy of a new antibiotic or vaccine can involve around 100 animals per candidate, in some cases causing “significant suffering”, the NC3RS pointed out. Using large datasets and computational tools to study disease biology and predict efficacy would reduce that number.
NephroTube: developing a multi-compartmental, microfluidic tissue assay that models the renal tubular injury observed in nephrotoxicity. The assay would mimic the 3D architecture of the kidney tubules with microfluidics and chip arrays, reproducing the tubular response to known nephrotoxicants. Drug-induced organ toxicity accounts for 30% of drugs failures in development. Within that figure, nephrotoxicity is responsible for 2% of failures at the preclinical stags and for 19% of failures in Phase III. A typical animal study to assess nephrotoxicity would use at least 26 rodents.
Inhalation Translation: the aim is to enable the longitudinal and non-invasive assessment of inflammation associated with drug toxicity in the same animal, rather than using multiple animals. This could reduce animal use by up to 90% at certain stages of drug discovery and development. The data obtained would be more reliable and less variable, leading to earlier go/no-go decisions on a drug candidate that might otherwise fail later in development, the NC3RS said. Few new drugs for chronic inflammatory diseases of the airways (e.g., asthma) have made it to the clinic over the last 50 years, with many performing well in preclinical animal studies but failing in humans due to lack of safety and/or efficacy.
InPulse: generating a physiologically-relevant 3D in vitro model to reduce the number of animals used in cardiotoxicity studies. A drug’s off-target effects on the cardiovascular system are one of the most common causes of attrition in both non-clinical and clinical settings, the NC3RS observed. While there is currently no human cell-derived in vitro approach available for cardiotoxicity studies, assays using iPS cell-derived cardiomyocytes have shown promise. These cells will form the basis of the challenge.