Key Points
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Animal models are important tools in the discovery and development of treatments for rare diseases, particularly given the small populations of patients in which to evaluate therapeutic candidates.
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Numerous animal models are available for research on rare diseases, from small transgenic rodents to large animals with naturally occurring disease.
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The European Medicines Agency (EMA)'s Committee for Orphan Medicinal Products has more than 10 years of experience in evaluating orphan medicinal products (OMPs) and is well placed to review the mammalian animal models, past and present, used for OMP development.
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Proof-of-concept studies of candidate therapeutics in animal models aim to evaluate their efficacy using clearly defined biomarkers and to confirm and/or clarify the anticipated mechanism of action, thus providing a foundation for initiating studies in patients with the orphan disease in question.
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In this article, we provide an in-depth discussion of the animal models that are available for proof-of-concept studies in metabolic, neuromuscular and ophthalmological diseases designated as orphan conditions.
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Aspects and concerns discussed relate to the choice of animal species available for study, the improvements to non-clinical experimental designs and the challenges of evaluating advanced therapies in the field of rare diseases.
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The overall aim of this article is to encourage more efficient and successful research and development of OMPs for rare diseases.
Abstract
Animal models are important tools in the discovery and development of treatments for rare diseases, particularly given the small populations of patients in which to evaluate therapeutic candidates. Here, we provide a compilation of mammalian animal models for metabolic, neuromuscular and ophthalmological orphan-designated conditions based on information gathered by the European Medicines Agency's Committee for Orphan Medicinal Products (COMP) since its establishment in 2000, as well as from a review of the literature. We discuss the predictive value of the models and their advantages and limitations with the aim of highlighting those that are appropriate for the preclinical evaluation of novel therapies, thereby facilitating further drug development for rare diseases.
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Acknowledgements
The authors specifically acknowledge the invaluable input of E. Héron (former member of the Committee for Orphan Medicinal Products (COMP), France), L. Håkansson (Medical Products Agency, Sweden) and J. P. Rocha (researcher at iMED.UL (Research Institute for Medicines and Pharmaceutical Sciences) and a professor at the University of Lisbon, Portugal).
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The views expressed in this article are the personal views of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.
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Vaquer, G., Dannerstedt, F., Mavris, M. et al. Animal models for metabolic, neuromuscular and ophthalmological rare diseases. Nat Rev Drug Discov 12, 287–305 (2013). https://doi.org/10.1038/nrd3831
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DOI: https://doi.org/10.1038/nrd3831
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