EURL ECVAM Literature Review Series on Advanced Non-Animal Models for Respiratory Diseases, Breast Cancer and Neurodegenerative Disorders

Simple Summary Directive 2010/63/EU on the protection of animals used for scientific purposes sets out the legal requirements for implementing the 'Three Rs' principles of Replacement, Reduction and Refinement of animal procedures. The final goal is to phase out animal testing and replace it with scientifically valid non-animal alternatives. According to the latest statistics, in 2019, the European Union used approximately 10 million animals in experimental procedures with about 70% of those used for biomedical research. However, effective new therapies for several serious diseases are still lacking. Over 90% of new drugs fail to progress to the market due mainly to a lack of efficacy or unexplained toxicity. This suggests that reliance on animal models is failing to identify novel therapies. In this context, the EU Reference Laboratory for alternatives to animal testing (EURLECVAM) of the European Commission's Joint Research Centre carried out a series of studies to produce a unique knowledge base that describes in detail non-animal models applied in several biomedical research areas. Here, a summary of the results on the areas of respiratory tract diseases, breast cancer and neurodegenerative disorders is described and commented on. In vivo models are used in biomedical research to reproduce human disease and develop new drugs. However, they do not mimic the disease as it occurs in humans, and their use has failed to identify novel therapies effective for many highly prevalent non-communicable diseases, such as Alzheimer's disease. Indeed, the clinical failure rate in drug development remains very high, with an overall likelihood of approval from Phase I of about 9.6%. On the other hand, human-based models, advanced imaging techniques and human epidemiological studies may increase our understanding of disease aetiology and pathogenesis and enable the advance of safe and effective therapies. Particularly when human tissues are used, they may produce faster, cheaper results, more predictive for humans, whilst yielding greater comprehensions of human biochemical processes. A first effort to collect existing knowledge about non-animal models of highly prevalent human diseases was made by the Joint Research Centre of the European Commission. The final aim was to identify and share information on the capabilities and limits of human-based models at different levels: scientific communities, universities and secondary schools, national committees for animal welfare and the public at large.